Interstitial telomeric loops and implications of the interaction between TRF2 and lamin A/C.
Abstract The protein-DNA complexes that compose the end of mammalian chromosomes-telomeres-serve to stabilize linear genomic DNA and are involved in cellular and organismal aging. One mechanism that protects telomeres from premature degradation is the formation of structures called t-loops, in which the single-stranded 3' overhang present at the terminal end of telomeres loops back and invades medial double-stranded telomeric DNA. We identified looped structures formed between terminal chromosome ends and interstitial telomeric sequences (ITSs), which are found throughout the human genome, that we have termed...
Source: Differentiation - June 18, 2018 Category: Research Authors: Smith ED, Garza-Gongora AG, MacQuarrie KL, Kosak ST Tags: Differentiation Source Type: research

Glucocorticoid-induced pancreatic-hepatic trans-differentiation in a human cell line in vitro.
Abstract The rodent pancreatic AR42J-B13 (B-13) cell line differentiates into non-replicative hepatocyte-like cells in response to glucocorticoid mediated via the glucocorticoid receptor (GR). The aims of this study were to identify a human cell line that responds similarly and investigate the mechanisms underpinning any alteration in differentiation. Exposing the human pancreatic adenocarcinoma (HPAC) cell line to 1-10 µM concentrations of dexamethasone (DEX) resulted an inhibition of proliferation, suppressed carcinoembryonic antigen expression, limited expression of pancreatic acinar and hepatic gene ex...
Source: Differentiation - May 22, 2018 Category: Research Authors: Fairhall EA, Leitch AC, Lakey AF, Probert PME, Richardson G, De Santis C, Wright MC Tags: Differentiation Source Type: research

Contrasting mechanisms of penile urethral formation in mouse and human.
Abstract This paper addresses the developmental mechanisms of formation of the mouse and human penile urethra and the possibility that two disparate mechanisms are at play. It has been suggested that the entire penile urethra of the mouse forms via direct canalization of the endodermal urethral plate. While this mechanism surely accounts for development of the proximal portion of the mouse penile urethra, we suggest that the distal portion of the mouse penile urethra forms via a series of epithelial fusion events. Through review of the recent literature in combination with new data, it is unlikely that the entire ...
Source: Differentiation - May 17, 2018 Category: Research Authors: Liu G, Liu X, Shen J, Sinclair A, Baskin L, Cunha GR Tags: Differentiation Source Type: research

Epha2 and Efna5 participate in lens cell pattern-formation.
Abstract Ephrin type-A receptor 2 (EPHA2) and one of its ligands, ephrin-A5 (EFNA5), have been associated with loss of eye lens transparency, or cataract, - an important cause of visual impairment. Here we show that mice functionally lacking EPHA2 (Epha2-null), EFNA5 (Efna5-null), or both receptor and ligand (Epha2/Efna5-null) consistently develop mostly transparent lenses with an internal refractive disturbance and a grossly disturbed cellular architecture. In situ hybridization localized Epha2 and Efna5 transcripts to lens epithelial cells and nascent fiber cells at the lens equator. In vivo labeling of Epha2-nu...
Source: Differentiation - May 17, 2018 Category: Research Authors: Zhou Y, Shiels A Tags: Differentiation Source Type: research

Tissue interactions and estrogenic response during human female fetal reproductive tract development.
Abstract The role of tissue interactions was explored to determine whether epithelial differentiation within the developing human reproductive tract is induced and specified by mesenchyme in tissue recombinants composed of mouse vaginal mesenchyme + human uterine tubal epithelium (mVgM+hTubE). The tissue recombinants were grown in DES-treated ovariectomized athymic mice. After 2-4 weeks of in vivo growth, several vaginal specific features were expressed in the human tubal epithelium. The mesenchyme-induced effects included morphological change as well as expression of several immunohistochemical markers. Although ...
Source: Differentiation - April 18, 2018 Category: Research Authors: Cunha GR, Kurita T, Cao M, Shen J, Cooke PS, Robboy SJ, Baskin LS Tags: Differentiation Source Type: research

Development of urogenital system in the Spix cavy: A model for studies on sexual differentiation.
This study documented, for the first time, the morphological patterns of differentiation of male and female genital organs of Spix cavy (Galea spixii) using histological and ultrastructural analyses, with immuno-localization of steroidogenic enzymes, cytochromes P450 aromatase (P450arom) and 17α-hydroxylase/17, 20-lyase (P450c17), involved in the synthesis of estrogens and androgens respectively throughout fetal sexual development. Undifferentiated gonads of Spix cavy develop into ovaries in females after 25 days of gestation (DG), exhibiting P450arom immunoreactivity. After 25 DG, paramesonephric ducts develop and f...
Source: Differentiation - April 13, 2018 Category: Research Authors: Dos Santos AC, Conley AJ, de Oliveira MF, de Assis Neto AC Tags: Differentiation Source Type: research

Differentiation of hepatocyte-like cells from human pluripotent stem cells using small molecules.
Abstract A variety of approaches have been developed for the derivation of hepatocyte-like cells from pluripotent stem cells. Currently, most of these strategies employ step-wise differentiation approaches with recombinant growth-factors or small-molecule analogs to recapitulate developmental signaling pathways. Here, we tested the efficacy of a small-molecule based differentiation protocol for the generation of hepatocyte-like cells from human pluripotent stem cells. Quantitative gene-expression, immunohistochemical, and western blot analyses for SOX17, FOXA2, CXCR4, HNF4A, AFP, indicated the stage-specific diffe...
Source: Differentiation - March 27, 2018 Category: Research Authors: Asumda FZ, Hatzistergos KE, Dykxhoorn DM, Jakubski S, Edwards J, Thomas E, Schiff ER Tags: Differentiation Source Type: research

Vitamin C-linker-conjugated tripeptide AHK stimulates BMP-2-induced osteogenic differentiation of mouse myoblast C2C12 cells.
Abstract Vitamin C-linker-conjugated Ala-His-Lys tripeptide (Vit C-AHK) is a derivative of Vitamin C-conjugated tripeptides, which were originally developed as a component of a product for collagen synthesis enhancement or human dermal fibroblast growth. Here, we investigated the effect of Vit C-AHK on bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Vit C-AHK enhanced proliferation of C2C12 cells and induction of BMP-2-induced alkaline phosphatase, a typical marker of osteoblast differentiation. Vit C-AHK also stimulated the phosphorylation and translocation of Smad1/...
Source: Differentiation - March 15, 2018 Category: Research Authors: Jung JI, Park KY, Lee Y, Park M, Kim J Tags: Differentiation Source Type: research

Transcriptome analysis identifies genes involved in sex determination and development of Xenopus laevis gonads.
Abstract Development of the gonads is a complex process, which starts with a period of undifferentiated, bipotential gonads. During this period the expression of sex-determining genes is initiated. Sex determination is a process triggering differentiation of the gonads into the testis or ovary. Sex determination period is followed by sexual differentiation, i.e. appearance of the first testis- and ovary-specific features. In Xenopus laevis W-linked DM-domain gene (DM-W) had been described as a master determinant of the gonadal female sex. However, the data on the expression and function of other genes participatin...
Source: Differentiation - March 2, 2018 Category: Research Authors: Piprek RP, Damulewicz M, Kloc M, Kubiak JZ Tags: Differentiation Source Type: research

Increased TERRA levels and RNase H sensitivity are conserved hallmarks of post-senescent survivors in budding yeast.
Abstract Cancer cells activate telomere maintenance mechanisms (TMMs) to bypass replicative senescence and achieve immortality by either upregulating telomerase or promoting homology-directed repair (HDR) at chromosome ends to maintain telomere length, the latter being referred to as ALT (Alternative Lengthening of Telomeres). In yeast telomerase mutants, the HDR-based repair of telomeres leads to the generation of 'survivors' that escape senescence and divide indefinitely. So far, yeast has proven to provide an accurate model to study the generation and maintenance of telomeres via HDR. Recently, it has been esta...
Source: Differentiation - February 16, 2018 Category: Research Authors: Misino S, Bonetti D, Luke-Glaser S, Luke B Tags: Differentiation Source Type: research

Short telomeres - A hallmark of heritable cardiomyopathies.
Abstract Cardiovascular diseases are the leading cause of death worldwide and the incidence increases with age. Genetic testing has taught us much about the pathogenic pathways that drive heritable cardiomyopathies. Here we discuss an unexpected link between shortened telomeres, a molecular marker of aging, and genetic cardiomyopathy. Positioned at the ends of chromosomes, telomeres are DNA repeats which serve as protective caps that shorten with each cell division in proliferative tissues. Cardiomyocytes are an anomaly, as they are largely non-proliferative post-birth and retain relatively stable telomere lengths...
Source: Differentiation - February 9, 2018 Category: Research Authors: Chang ACY, Blau HM Tags: Differentiation Source Type: research

Telomeres and telomerase in heart regeneration.
Abstract Although recent advances have overturned the old view of the human heart as an inert postmitotic organ, it is clear that the adult heart´s capacity to regenerate after an ischemic episode is very limited. Unlike humans, zebrafish and other lower vertebrates vigorously regenerate damaged myocardium after cardiac injury. Understanding how the zebrafish is able to conserve life-long cardiac regeneration capacity while mammals lose it soon after birth is crucial for the development of new treatments for myocardial infarction. Mammals and lower vertebrates differ markedly in their rates of cardiomyocyte ...
Source: Differentiation - February 3, 2018 Category: Research Authors: Aix E, Gallinat A, Flores I Tags: Differentiation Source Type: research

Stretching, scrambling, piercing and entangling: Challenges for telomeres in mitotic and meiotic chromosome segregation.
Abstract The consequences of telomere loss or dysfunction become most prominent when cells enter the nuclear division stage of the cell cycle. At this climactic stage when chromosome segregation occurs, telomere fusions or entanglements can lead to chromosome breakage, wreaking havoc on genome stability. Here we review recent progress in understanding the mechanisms of detangling and breaking telomere associations at mitosis, as well as the unique ways in which telomeres are processed to allow regulated sister telomere separation. Moreover, we discuss unexpected roles for telomeres in orchestrating nuclear envelop...
Source: Differentiation - February 1, 2018 Category: Research Authors: Hou H, Cooper JP Tags: Differentiation Source Type: research

How stem cells keep telomeres in check.
Abstract In multicellular organisms, regulation of telomere length in pluripotent stem cells is critical to ensure organism development and survival. Telomeres consist of repetitive DNA that are progressively lost with each cellular division. When telomeres become critically short, they activate a DNA damage response that results in cell cycle arrest. To counteract telomere attrition, pluripotent stem cells are equipped with telomere elongation mechanisms that ensure prolonged proliferation capacity and self-renewal capacity. Excessive telomere elongation can also be deleterious and is counteracted by a rapid telo...
Source: Differentiation - February 1, 2018 Category: Research Authors: Li JSZ, Denchi EL Tags: Differentiation Source Type: research

Dysfunctional telomeres and hematological disorders.
Abstract Telomere biology disorders, which are characterized by telomerase activity haploinsufficiency and accelerated telomere shortening, most commonly manifest as degenerative diseases. Tissues with high rates of cell turnover, such as those in the hematopoietic system, are particularly vulnerable to defects in telomere maintenance genes that eventually culminate in bone marrow (BM) failure syndromes, in which the BM cannot produce sufficient new blood cells. Here, we review how telomere defects induce degenerative phenotypes across multiple organs, with particular focus on how they impact the hematopoietic ste...
Source: Differentiation - January 4, 2018 Category: Research Authors: Fiorini E, Santoni A, Colla S Tags: Differentiation Source Type: research

Telomeres in cancer.
Abstract Telomere shortening as a consequence of cell divisions during aging and chronic diseases associates with an increased cancer risk. Experimental data revealed that telomere shortening results in telomere dysfunction, which in turn affects tumorigenesis in two ways. First, telomere dysfunction suppresses tumor progression by the activation of DNA damage checkpoints, which induce cell cycle arrest (senescence) or apoptosis, as well as by inducing metabolic compromise and activation of immune responses directed against senescent cells. Second, telomere dysfunction promotes tumorigenesis by inducing chromosoma...
Source: Differentiation - December 21, 2017 Category: Research Authors: Gunes C, Avila AI, Rudolph KL Tags: Differentiation Source Type: research

The role of gastrulation brain homeobox 2 (gbx2) in the development of the ventral telencephalon in zebrafish embryos.
In this study, we addressed this issue in zebrafish (Danio rerio) first by carefully examining gbx2 expression in the developing forebrain. We showed that gbx2 was expressed in the telencephalon during late somitogenesis, from 18h post-fertilization (hpf) to 24 hpf, and in the thalamic primordium after 26 hpf. In contrast, another gbx gene, gbx1, was expressed in the anterior-most ventral telencephalon after 36 hpf. Thus, the expression patterns of these two gbx genes did not overlap, arguing against their redundant function in the forebrain. Two-color fluorescence in situ hybridization (FISH) showed close relationships be...
Source: Differentiation - December 21, 2017 Category: Research Authors: Wang Z, Nakayama Y, Tsuda S, Yamasu K Tags: Differentiation Source Type: research

Impact of oxidative stress on telomere biology.
Abstract Telomere integrity is essential for genome stability and it regulates cell proliferation and tissue renewal. Several lines of evidence indicate that telomeres are particularly sensitive to oxidative damage. Moreover, recent studies demonstrate striking inhibitory effects of oxidative damage on telomerase activity. On the other hand, several mechanisms have been uncovered that either counteract oxidative damage at telomeres or remove the modified lesions. Here, we review the current understanding of oxidative damage and protection of telomeric DNA. We discuss how oxidative telomeric lesions impact on telom...
Source: Differentiation - December 14, 2017 Category: Research Authors: Ahmed W, Lingner J Tags: Differentiation Source Type: research

Mechanisms of epithelial thickening due to IL-1 signalling blockade and TNF- α administration differ during wound repair and regeneration.
Mechanisms of epithelial thickening due to IL-1 signalling blockade and TNF-α administration differ during wound repair and regeneration. Differentiation. 2017 Dec 12;99:10-20 Authors: Abarca-Buis RF, Martínez-Jiménez A, Vera-Gómez E, Contreras-Figueroa ME, Garciadiego-Cázares D, Paus R, Robles-Tenorio A, Krötzsch E Abstract IL-1 and TNF-α are always present during wound repair, but their pleiotropic and synergistic effects are incompletely understood. In this work, we evaluated the role of IL-1 in wound repair, and examined whether TNF-α administrati...
Source: Differentiation - December 12, 2017 Category: Research Authors: Abarca-Buis RF, Martínez-Jiménez A, Vera-Gómez E, Contreras-Figueroa ME, Garciadiego-Cázares D, Paus R, Robles-Tenorio A, Krötzsch E Tags: Differentiation Source Type: research

Long-range telomere regulation of gene expression: Telomere looping and telomere position effect over long distances (TPE-OLD).
Abstract The human cellular reverse transcriptase, telomerase, is very tightly regulated in large long-lived species. Telomerase is expressed during early human fetal development, is turned off in most adult tissues, and then becomes reactivated in almost all human cancers. However, the exact mechanism regulating these switches in expression are not known. We recently described a phenomenon where genes are regulated by telomere length dependent loops (telomere position effects over long distances; TPE-OLD). The hTERT gene is ~ 1.2Mb from the human chromosome 5p end. We observed that when telomeres are long hTERT g...
Source: Differentiation - November 22, 2017 Category: Research Authors: Kim W, Shay JW Tags: Differentiation Source Type: research

RAR β2-dependent signaling represses neuronal differentiation in mouse ES cells.
RARβ2-dependent signaling represses neuronal differentiation in mouse ES cells. Differentiation. 2017 Nov 10;98:55-61 Authors: Kona SL, Shrestha A, Yi X, Joseph S, Barona HM, Martinez-Ceballos E Abstract Embryonic Stem (ES) cells are pluripotent cells that can be induced to differentiate into cells of all three lineages: mesoderm, endoderm, and ectoderm. In culture, ES cells can be differentiated into mature neurons by treatment with Retinoic Acid (RA) and this effect is mediated mainly through the activation of the RA nuclear receptors (RAR α, β, and γ), and their isoforms. Howe...
Source: Differentiation - November 10, 2017 Category: Research Authors: Kona SL, Shrestha A, Yi X, Joseph S, Barona HM, Martinez-Ceballos E Tags: Differentiation Source Type: research

Xenografted tissue models for the study of human endometrial biology.
The objective of this review is to summarize the recent developments and work on these in vivo endometrial research models. The in vivo recombinant tissue models in which wild-type endometrial cells are combined with endometrial cells from a gene-targeted mouse strain followed by xenografting to host mice have been critical in confirming the significance of paracrine signaling between the epithelium and stroma in the growth regulation of the endometrium. Additionally, these studies have uncovered differences between the mouse and human, emphasizing the need for the development of experimental models specifically of the hum...
Source: Differentiation - November 10, 2017 Category: Research Authors: Kuokkanen S, Zhu L, Pollard JW Tags: Differentiation Source Type: research

Involvement of the Mab21l1 gene in calvarial osteogenesis.
In this study, we observed that mice lacking Mab21l1 displayed an unclosed fontanelle, suggesting impaired calvarial bone development. Cells isolated from the calvaria of these mice showed a greater osteoblast differentiation potential as evidenced by the abundance of mineralized bone nodules and higher expression levels of osteogenic markers than wild-type cells. Mab21l1-/- osteoblasts also expressed higher levels of adipocyte genes and interferon-regulated genes at early stages of osteogenesis. Rankl/Opg expression levels were also higher in Mab21l1-/- osteoblasts than in wild-type cells. These data suggest that Mab21l1 ...
Source: Differentiation - November 9, 2017 Category: Research Authors: Nguyen D, Yamada R, Yoshimitsu N, Oguri A, Kojima T, Takahashi N Tags: Differentiation Source Type: research

Response of xenografts of developing human female reproductive tracts to the synthetic estrogen, diethylstilbestrol.
Abstract Human female fetal reproductive tracts 9.5-22 weeks of gestation were grown for 1 month in ovariectomized athymic adult female mouse hosts that were either untreated or treated continuously with diethylstilbestrol (DES) via subcutaneous pellet. Normal morphogenesis and normal patterns of differentiation marker expression (KRT6, KRT7, KRT8, KRT10, KRT14, KRT19, ESR1, PGR, TP63, RUNX1, ISL1, HOXA11 and α-ACT2) were observed in xenografts grown in untreated hosts and mimicked observations of previously reported (Cunha et al., 2017) non-grafted specimens of comparable age. DES elicited several notable m...
Source: Differentiation - October 4, 2017 Category: Research Authors: Cunha GR, Kurita T, Cao M, Shen J, Robboy SJ, Baskin L Tags: Differentiation Source Type: research

Renal Subcapsular xenografing of human fetal external genital tissue - A new model for investigating urethral development.
Abstract In this paper, we introduce our novel renal subcapsular xenograft model for the study of human penile urethral and clitoral development. We grafted fifteen intact fetal penes and clitorides 8-11 weeks fetal age under the renal capsules of gonadectomized athymic mice. The mice were treated with a subcutaneous pellet of dihydrotestosterone (DHT), diethylstilbestrol (DES) or untreated with hormones. Xenografts were harvested after fourteen days of growth and analyzed via serial histologic sectioning and immunostaining for Ki-67, cytokeratins 6, 7 and 10, uroplakin and the androgen receptor. Non-grafted speci...
Source: Differentiation - September 22, 2017 Category: Research Authors: Isaacson D, Shen J, Cao M, Sinclair A, Yue X, Cunha G, Baskin L Tags: Differentiation Source Type: research

Xenotransplantation as a model for human testicular development.
Abstract The developing male reproductive system may be sensitive to disruption by a wide range of exogenous 'endocrine disruptors'. In-utero exposure to environmental chemicals and pharmaceuticals have been hypothesized to have an impact in the increasing incidence of male reproductive disorders. The vulnerability to adverse effects as a consequence of such exposures is elevated during a specific 'window of susceptibility' in fetal life referred to as the masculinisation programing window (MPW). Exposures that occur during prepuberty, such as chemotherapy treatment for cancer during childhood, may also affect fut...
Source: Differentiation - September 13, 2017 Category: Research Authors: Hutka M, Smith LB, Mitchell RT Tags: Differentiation Source Type: research

Prostate cancer xenografts and hormone induced prostate carcinogenesis.
Abstract Despite the advancement of transgenic and gene knockout animal models in the prostate cancer research, there is still a need for utilizing xenograft models. Xenografts can be grown in multiple sites/organs within immunocompromised animals such as mice and rats. Although prostate xenografts have been derived from many species, human cells and tissues are the most commonly used due to their potential clinical significance. Xenograft models that progress from one state or stage to another are commonly used to address important scientific questions including malignant transformation, metastatic spread, and ca...
Source: Differentiation - September 8, 2017 Category: Research Authors: McLean DT, Strand DW, Ricke WA Tags: Differentiation Source Type: research

New insights into human female reproductive tract development.
We present a detailed review of the embryonic and fetal development of the human female reproductive tract utilizing specimens from the 5th through the 22nd gestational week. Hematoxylin and eosin (H&E) as well as immunohistochemical stains were used to study the development of the human uterine tube, endometrium, myometrium, uterine cervix and vagina. Our study revisits and updates the classical reports of Koff (1933) and Bulmer (1957) and presents new data on development of human vaginal epithelium. Koff proposed that the upper 4/5ths of the vagina is derived from Müllerian epithelium and the lower 1/5th derived...
Source: Differentiation - August 11, 2017 Category: Research Authors: Robboy SJ, Kurita T, Baskin L, Cunha GR Tags: Differentiation Source Type: research

Extrinsic control of Wnt signaling in the intestine.
Abstract The canonical Wnt/β-catenin signaling pathway is a central regulator of development and tissue homeostasis. In the intestine, Wnt signaling is primarily known as the principal organizer of epithelial stem cell identity and proliferation. Within the last decade, numerous scientific breakthroughs have shed light on epithelial self-organization in the gut, and organoids are now routinely used to study stem cell biology and intestinal pathophysiology. The contribution of non-epithelial cells to Wnt signaling in the gut has received less attention. However, there is mounting evidence that stromal cells ar...
Source: Differentiation - August 5, 2017 Category: Research Authors: Koch S Tags: Differentiation Source Type: research

Targeting phenotypic heterogeneity in benign prostatic hyperplasia.
Abstract Benign prostatic hyperplasia and associated lower urinary tract symptoms remain difficult to treat medically, resulting in hundreds of thousands of surgeries performed annually in elderly males. New therapies have not improved clinical outcomes since alpha blockers and 5 alpha reductase inhibitors were introduced in the 1990s. An underappreciated confounder to identifying novel targets is pathological heterogeneity. Individual patients display unique phenotypes, composed of distinct cell types. We have yet to develop a cellular or molecular understanding of these unique phenotypes, which has led to failur...
Source: Differentiation - August 4, 2017 Category: Research Authors: Strand DW, Costa DN, Francis F, Ricke WA, Roehrborn CG Tags: Differentiation Source Type: research

Production of high purity alveolar-like cells from iPSCs through depletion of uncommitted cells after AFE induction.
In conclusion, depletion of uncommitted cells after AFE induction, improves terminal differentiation of alveolar cells from 31% to 74%. PMID: 28802115 [PubMed - as supplied by publisher] (Source: Differentiation)
Source: Differentiation - August 3, 2017 Category: Research Authors: Mitchell A, Drinnan CT, Jensen T, Finck C Tags: Differentiation Source Type: research

Effect of matrix stiffness on the proliferation and differentiation of umbilical cord mesenchymal stem cells.
Abstract Mesenchymal stem cells (MSCs) are a compatible cellular alternative for regenerative medicine and tissue engineering because of their powerful multipotency. Matrix stiffness plays a profound role on stem cell behavior. Nevertheless, the effect of matrix stiffness on umbilical cordmesenchymal stem cells (UC-MSCs) remains unexplored. To conduct an in-depth exploration, we cultured UC-MSCs on different stiffness (Young's modulus: 13-16, 35-38, 48-53, and 62-68 kPa) polyacrylamide gels coated with fibronectin. We found that the proliferation and adhesion of UC-MSCs varied when cultured on the different matric...
Source: Differentiation - July 21, 2017 Category: Research Authors: Xu J, Sun M, Tan Y, Wang H, Wang H, Li P, Xu Z, Xia Y, Li L, Li Y Tags: Differentiation Source Type: research

Skin regeneration in three dimensions, current status, challenges and opportunities.
g F Abstract Skin regeneration is a life-saving need for many patients, whom list is stretched from burn victims to motor-car accidents. Spraying cells, either keratinocytes or stem cells, were associated with variable results and, in many cases, unfavorable outcomes. As the spatial configuration of the skin is distinctive, many trials investigated the bio-printing or the construction of three dimensional skin models where different layers of the skin were preserved. Although some of these models showed the histological configuration of the skin, their acceptance by the wound was questionable as a consequence of d...
Source: Differentiation - June 15, 2017 Category: Research Authors: El-Serafi AT, El-Serafi IT, Elmasry M, Steinvall I, Sjöberg F Tags: Differentiation Source Type: research

Hepatocellular differentiation status is characterized by distinct subnuclear localization and form of the chanzyme TRPM7.
Abstract The channel-kinase TRPM7 is important for the survival, proliferation, and differentiation, of many cell types. Both plasma membrane channel activity and kinase function are implicated in these roles. Channel activity is greater in less differentiated hepatoma cells compared with non-dividing, terminally differentiated adult hepatocytes, suggesting differences in protein expression and/or localization. We used electrophysiological and immunofluorescence approaches to establish whether hepatocellular differentiation is associated with altered TRPM7 expression. Mean outward current decreased by 44% in WIF-B...
Source: Differentiation - June 10, 2017 Category: Research Authors: Ogunrinde A, Pereira RD, Beaton N, Lam DH, Whetstone C, Hill CE Tags: Differentiation Source Type: research

Ascorbic acid-mediated enhanced cardiomyocyte differentiation of mouse ES-cells involves interplay of DNA methylation and multiple-signals.
Abstract Embryonic stem cells (ES-cells) provide a good model system to study lineage-specific differentiation. Though, the differentiation of ES-cells to cardiomyocytes is documented, a clear understanding of the molecular mechanism of differentiation and improved functional-differentiation efficiency are yet to be achieved. In this regard, ascorbic acid (Aa) is shown to be one of the effective cardiac inducers in ES-cells. But, its mechanism is poorly understood. We therefore, investigated the mechanism of Aa-mediated cardiomyocyte differentiation of ES-cells. Here, we describe the potential involvement of epige...
Source: Differentiation - May 10, 2017 Category: Research Authors: Abbey D, Seshagiri PB Tags: Differentiation Source Type: research

Phosphate regulates chondrogenesis in a biphasic and maturation-dependent manner.
Abstract Inorganic phosphate (Pi) has been recognized as an important signaling molecule that modulates chondrocyte maturation and cartilage mineralization. However, conclusive experimental evidence for its involvement in early chondrogenesis is still lacking. Here, using high-density monolayer (2D) and pellet (3D) culture models of chondrogenic ATDC5 cells, we demonstrate that the cell response to Pi does not correlate with the Pi concentration in the culture medium but is better predicted by the availability of Pi on a per cell basis (Pi abundance). Both culture models were treated with ITS+, 10mM β-glycero...
Source: Differentiation - May 8, 2017 Category: Research Authors: Wu B, Durisin EK, Decker JT, Ural EE, Shea LD, Coleman RM Tags: Differentiation Source Type: research

Different combinations of growth factors for the tenogenic differentiation of bone marrow mesenchymal stem cells in monolayer culture and in fibrin-based three-dimensional constructs.
This study aimed to investigate the tenogenic differentiation of rabbit BMSCs by testing the combination of bone morphogenetic proteins (BMP-12 and 14) with transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF) both in 2D and 3D cultures within fibrin-based constructs. After 7 and 14 days, the tenogenic differentiation was assessed by analyzing cell metabolism and collagen content, the gene expression of tenogenic markers and the histological cell distribution and collagen deposition within 3D constructs. Our results demonstrated that the association of BMP-14 with TGF-β3 and VEGF ...
Source: Differentiation - March 15, 2017 Category: Research Authors: Bottagisio M, Lopa S, Granata V, Talò G, Bazzocchi C, Moretti M, Barbara Lovati A Tags: Differentiation Source Type: research

The small GTPase Arf6 regulates sea urchin morphogenesis.
This study examines the function of Arf6 in mediating cellular morphogenesis in early development. We dissect the function of Arf6 with a loss-of-function morpholino and constitutively active Arf6-Q67L construct. We focus on the two cell types that undergo active directed migration: the primary mesenchyme cells (PMCs) that give rise to the sea urchin skeleton and endodermal cells that form the gut. Our results indicate that Arf6 plays an important role in skeleton formation and PMC migration, in part due to its ability to remodel actin. We also found that embryos injected with Arf6 morpholino have gastrulation defects and ...
Source: Differentiation - February 1, 2017 Category: Research Authors: Stepicheva NA, Dumas M, Kobi P, Donaldson JG, Song JL Tags: Differentiation Source Type: research

Hierarchical transcriptional profile of urothelial cells development and differentiation.
Abstract The urothelial lining of the lower urinary tract is the most efficient permeability barrier in animals, exhibiting a highly differentiated phenotype and a remarkable regenerative capacity upon wounding. During development and possibly during repair, cells undergo a sequence of hierarchical transcriptional events that mark the transition of these cells from the least differentiated urothelial phenotype characteristic of the basal cell layer, to the most differentiated cellular phenotype characteristic of the superficial cell layer. Unraveling normal urothelial differentiation program is essential to uncove...
Source: Differentiation - January 26, 2017 Category: Research Authors: Al-Kurdi B Tags: Differentiation Source Type: research

EGF and hydrocortisone as critical factors for the co-culture of adipogenic differentiated ASCs and endothelial cells.
Abstract In vitro composed vascularized adipose tissue is and will continue to be in great demand e.g. for the treatment of extensive high-graded burns or the replacement of tissue after tumor removal. Up to date, the lack of adequate culture conditions, mainly a culture medium, decelerates further achievements. In our study, we evaluated the influence of epidermal growth factor (EGF) and hydrocortisone (HC), often supplemented in endothelial cell (EC) specific media, on the co-culture of adipogenic differentiated adipose-derived stem cells (ASCs) and microvascular endothelial cells (mvECs). In ASCs, EGF and HC ar...
Source: Differentiation - January 19, 2017 Category: Research Authors: Volz AC, Huber B, Schwandt AM, Kluger PJ Tags: Differentiation Source Type: research

Induced differentiation of human gingival fibroblasts into VSMC-like cells.
In conclusion, the data indicated that HGFs could differentiate to VSMC-like cells with typical VSMC morphologic, ultrastructural, and immunological characteristics via induction with PDGF-BB and TGF-β1. PMID: 28107746 [PubMed - as supplied by publisher] (Source: Differentiation)
Source: Differentiation - January 16, 2017 Category: Research Authors: Liu X, Wang J, Dong F, Li H, Hou Y Tags: Differentiation Source Type: research

Nuclear envelope localization of LEMD2 is developmentally dynamic and lamin A/C dependent yet insufficient for heterochromatin tethering.
Abstract Peripheral heterochromatin in mammalian nuclei is tethered to the nuclear envelope by at least two mechanisms here referred to as the A- and B-tethers. The A-tether includes lamins A/C and additional unknown components presumably INM protein(s) interacting with both lamins A/C and chromatin. The B-tether includes the inner nuclear membrane (INM) protein Lamin B-receptor, which binds B-type lamins and chromatin. Generally, at least one of the tethers is always present in the nuclear envelope of mammalian cells. Deletion of both causes the loss of peripheral heterochromatin and consequently inversion of the...
Source: Differentiation - January 1, 2017 Category: Research Authors: Thanisch K, Song C, Engelkamp D, Koch J, Wang A, Hallberg E, Foisner R, Leonhardt H, Stewart CL, Joffe B, Solovei I Tags: Differentiation Source Type: research

Flutamide-induced hypospadias in rats: A critical assessment.
Abstract This paper provides the first detailed description of flutamide-induced hypospadias in the rat based upon wholemount, histologic, three-dimensional reconstruction, scanning electron microscopic, and immunocytochemical analysis. The penile malformations elicited by this potent anti-androgen include a substantial proximal shift in the urethral meatus that clearly conforms to the definition of hypospadias based upon specific morphological criteria for this malformation. Through examination of the normal penile development and flutamide-induced abnormal penile development observed in prenatally oil- and fluta...
Source: Differentiation - December 29, 2016 Category: Research Authors: Sinclair AW, Cao M, Pask A, Baskin L, Cunha GR Tags: Differentiation Source Type: research

Disruption of homeobox containing gene, hbx9 results in the deregulation of prestalk cell patterning in Dictyostelium discoideum.
Abstract We have earlier classified the homeobox containing genes from Dictyostelium discoideum and identified 5 genes belonging to the TALE class. Here, we have characterized hbx9, a member of TALE class. In situ hybridization results show it to be preferentially expressed in the prestalkA (pstA) cells but not in the prestalkO (pstO) cells. Disruption of the hbx9 gene in Ax2 cells delay initiation of development and also slows cell proliferation. There was decreased cadA expression during the development of hbx9(-) cells, which results in inappropriate cell contacts, altered cell motility and patterning propertie...
Source: Differentiation - December 23, 2016 Category: Research Authors: Mishra H, Bhadoriya P, Saran S Tags: Differentiation Source Type: research

Focus on the role of Caveolin and Cavin protein families in liposarcoma.
Abstract The identification of ancillary biomarkers useful to improve diagnosis is a major challenge for adipocytic liposarcoma (LPS), the most common type among soft tissue sarcomas affecting adulthood. Recent findings have reported the expression of some proteins belonging to Caveolin and Cavin families as a critical hallmark distinctive of the least aggressive, well-differentiated LPS tumors. These proteins are involved in the biogenesis, morphology and function of caveolae, minute bulb-shaped domains of the plasma membrane that play a crucial role in the adipose tissue by controlling hormone-dependent uptake o...
Source: Differentiation - December 6, 2016 Category: Research Authors: Codenotti S, Vezzoli M, Monti E, Fanzani A Tags: Differentiation Source Type: research

Loss of Rearranged L-Myc Fusion (RLF) results in defects in heart development in the mouse.
This study provides the first evidence that RLF is required for normal heart development in the mouse. The heart morphological defects present at high penetrance in Rlf mutants are consistent with features of LVNC in humans, and molecular analysis identified attenuated JAGGED 1 expression and NOTCH signalling as likely contributors to these defects. Our study highlights the importance of RLF-dependent epigenetic modifications to DNA for maintaining correct gene regulatory network and intercellular signalling interactions during heart chamber and septal development. Further investigations are needed to define the biochemica...
Source: Differentiation - December 4, 2016 Category: Research Authors: Bourke LM, Del Monte-Nieto G, Outhwaite JE, Bharti V, Pollock PM, Simmons DG, Adam A, Hur SS, Maghzal GJ, Whitelaw E, Stocker R, Suter CM, Harvey RP, Harten SK Tags: Differentiation Source Type: research

Hydronephrosis in the Wnt5a-ablated kidney is caused by an abnormal ureter-bladder connection.
This study shows that Wnt5a is not required for development of the renal medulla and that loss of the renal medullary region in the Wnt5a-deleted kidney is caused by an abnormal ureter-bladder connection. PMID: 27923152 [PubMed - as supplied by publisher] (Source: Differentiation)
Source: Differentiation - December 2, 2016 Category: Research Authors: Yun K, Perantoni AO Tags: Differentiation Source Type: research

Transformation of jaw muscle satellite cells to cardiomyocytes.
Abstract In the embryo a population of progenitor cells known as the second heart field forms not just parts of the heart but also the jaw muscles of the head. Here we show that it is possible to take skeletal muscle satellite cells from jaw muscles of the adult mouse and to direct their differentiation to become heart muscle cells (cardiomyocytes). This is done by exposing the cells to extracellular factors similar to those which heart progenitors would experience during normal embryonic development. By contrast, cardiac differentiation does not occur at all from satellite cells isolated from trunk and limb muscl...
Source: Differentiation - December 1, 2016 Category: Research Authors: Daughters RS, Keirstead SA, Slack JM Tags: Differentiation Source Type: research

Beta-catenin and estrogen signaling collaborate to drive cyclin D1 expression in developing mouse prostate.
Abstract Androgen, beta-catenin (CTNNB1), and estrogen pathways stimulate proliferative growth of developing mouse prostate but how these pathways interact is not fully understood. We previously found that androgens induce CTNNB1 signaling in mouse urogenital sinus (UGS) epithelium from which prostatic ductal epithelium derives. Others have shown that low estradiol concentrations induce UGS epithelial proliferative growth. Here, we found that CTNNB1 signaling overlaps cyclin D1 (CCND1) expression in prostatic buds and we used a genetic approach to test whether CTNNB1 signaling induces CCND1 expression. We observed...
Source: Differentiation - December 1, 2016 Category: Research Authors: Mulligan WA, Wegner KA, Keil KP, Mehta V, Taketo MM, Vezina CM Tags: Differentiation Source Type: research

Fam3c modulates osteogenic differentiation by down-regulating Runx2.
In this study, we examined the role of Fam3c during osteoblast differentiation. Fam3c was found to be expressed during osteogenic differentiation of both primary bone marrow stromal cells and MC3T3-E1 pre-osteoblasts. In differentiating osteoblasts, knockdown of Fam3c increased alkaline phosphatase expression and activity whereas overexpression of Fam3c reduced it. Furthermore, overexpression of Fam3c caused reduction of Runx2 expression at both mRNA and protein levels. Fam3c was localized in the cytoplasm and it was not secreted outside the cell during osteoblast differentiation and therefore, may function intracellularly...
Source: Differentiation - November 29, 2016 Category: Research Authors: Bendre A, Büki KG, Määttä JA Tags: Differentiation Source Type: research