GSK3 inhibition, but not epigenetic remodeling, mediates efficient derivation of germline embryonic stem cells from nonobese diabetic mice
We examined small molecule inhibition of glycogen synthase kinase 3 (GSK3) to block spontaneous cell differentiation and promote pluripotency persistence. Here we show a single pharmacological GSK3 inhibitor, 6-bromoindirubin-3′-oxime (BIO), in combination with leukemia inhibition factor (LIF), promoted generation of stable NOD ESC lines at>80% efficiency. Significantly, expansion of the established NOD ESC lines no longer required treatment with BIO. These NOD ESC lines contributed to chimeric mice and transmitted to germline progeny that spontaneously developed diabetes. By contrast, 5-aza-2′-deoxycytidine...
Source: Stem Cell Research - July 5, 2018 Category: Stem Cells Source Type: research

Generation of a human induced pluripotent stem cell line, KSCBi003-A, from human adipose tissue-derived mesenchymal stem cells using a chromosomal integration-free system
Publication date: August 2018Source: Stem Cell Research, Volume 31Author(s): Hye Young Choi, So-Jung Kim, Gue Youn Go, Ara Kwon, Young Sam Im, Hye-Yeong Ha, Jin Tae Hong, Ji-won Jung, Soo Kyung KooAbstractWe generated a human induced pluripotent stem cell (hiPSC) line, KSCBi003-A, from adipose tissue-derived mesenchymal stem cells (Ad-MSCs) using a Sendai virus-based gene delivery system. We confirmed that the KSCBi003-A has a normal karyotype and short tandem repeat (STR)-based identities that match the parent cells. We also confirmed that the cell line expresses pluripotent stem cell markers such as Nanog, OCT4, SSEA-4, ...
Source: Stem Cell Research - July 5, 2018 Category: Stem Cells Source Type: research

A fast method to reprogram and CRISPR/Cas9 gene editing from erythroblasts
Publication date: Available online 4 July 2018 Source:Stem Cell Research Author(s): Uirá Souto Melo, Felipe de Souza Leite, Silvia Costa, Carla Rosenberg, Mayana Zatz An efficient one-step procedure to reprogram fibroblasts into human induced pluripotent stem cells (hiPSC) and perform CRISPR/Cas9 gene editing simultaneously was recently reported. Here we show that such simultaneous reprogramming and gene editing can be efficiently done from erythroblasts. We successfully obtained human induced pluripotent stem cells colonies together with in frame and out of frame CAPN1 mutations in one or both alleles. We did not ...
Source: Stem Cell Research - July 4, 2018 Category: Stem Cells Source Type: research

Derivation and molecular characterization of pancreatic differentiated MODY1-iPSCs
Publication date: Available online 26 June 2018 Source:Stem Cell Research Author(s): Carmel Braverman-Gross, Neta Nudel, Daniel Ronen, Nicola L. Beer, Mark I. McCarty, Nissim Benvenisty Maturity onset diabetes of the young (MODY) is a hereditary form of diabetes mellitus presenting at childhood or adolescence, which eventually leads to pancreatic β-cells dysfunction. The underlying genetic basis of MODY disorders is haploinsufficiency, where loss–of-function mutations in a single allele cause the diabetic phenotype in heterozygous patients. MODY1 is a type of MODY disorder resulting from a mutation in the trans...
Source: Stem Cell Research - June 27, 2018 Category: Stem Cells Source Type: research

Generation of a human induced pluripotent stem cell line, KSCBi003-A, from human adipose tissue-derived mesenchymal stem cells using a chromosomal integration-free system
Publication date: Available online 27 June 2018 Source:Stem Cell Research Author(s): Hye Young Choi, So-Jung Kim, Gue Youn Go, Ara Kwon, Young Sam Im, Hye-Yeong Ha, Jin Tae Hong, Ji-won Jung, Soo Kyung Koo We generated a human induced pluripotent stem cell (hiPSC) line, KSCBi003-A, from adipose tissue-derived mesenchymal stem cells (Ad-MSCs) using a Sendai virus-based gene delivery system. We confirmed that the KSCBi003-A has a normal karyotype and short tandem repeat (STR)-based identities that match the parent cells. We also confirmed that the cell line expresses pluripotent stem cell markers such as Nanog, OCT4, SSEA-4...
Source: Stem Cell Research - June 27, 2018 Category: Stem Cells Source Type: research

GSK3 inhibition, but not epigenetic remodeling, mediates efficient derivation of germline embryonic stem cells from nonobese diabetic mice
We examined small molecule inhibition of glycogen synthase kinase 3 (GSK3) to block spontaneous cell differentiation and promote pluripotency persistence. Here we show a single pharmacological GSK3 inhibitor, 6-bromoindirubin-3′-oxime (BIO), in combination with leukemia inhibition factor (LIF), promoted generation of stable NOD ESC lines at >80% efficiency. Significantly, expansion of the established NOD ESC lines no longer required treatment with BIO. These NOD ESC lines contributed to chimeric mice and transmitted to germline progeny that spontaneously developed diabetes. By contrast, 5-aza-2′-deoxycyt...
Source: Stem Cell Research - June 22, 2018 Category: Stem Cells Source Type: research

Endothelial cells instruct liver specification of embryonic stem cell-derived endoderm through endothelial VEGFR2 signaling and endoderm epigenetic modifications
This study provides an efficient 2D platform modelling the endothelial cell niche crosstalk with endoderm, and reveals mechanisms by which endothelial cells promote hepatic specification of mouse ESC-derived endoderm cells through endothelial VEGFR2 activation and endoderm epigenetic modifications. (Source: Stem Cell Research)
Source: Stem Cell Research - June 22, 2018 Category: Stem Cells Source Type: research

Generation of an induced pluripotent stem cell line from a patient with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP): HIHCNi003-A
Publication date: Available online 20 June 2018 Source:Stem Cell Research Author(s): Stefanie Nicole Hayer, Yvonne Schelling, Philip Hoeflinger, Stefan Hauser, Ludger Schöls An induced pluripotent stem cell line, HIHCNi003-A (iPSC-ALSP), was created from a skin biopsy of a patient with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) caused by a heterozygous c.2512G > C, p.Val838Leu mutation in the CSF1R gene. Skin fibroblasts were reprogrammed using episomal plasmids carrying hOCT4, hSOX2, hKLF4, hL-MYC, and hLIN28. The iPSC-ALSP line exhibits chromosomal stability with cons...
Source: Stem Cell Research - June 21, 2018 Category: Stem Cells Source Type: research

A naked mole-rat iPSC line expressing drug-inducible mouse pluripotency factors developed from embryonic fibroblasts
Publication date: Available online 20 June 2018 Source:Stem Cell Research Author(s): Sang-Goo Lee, Aleksei E. Mikhalchenko, Sun Hee Yim, Vadim N. Gladyshev Naked mole rats (NMRs, Heterocephalus glaber) are long-lived, cancer-resistant rodents. Here, we report the development of an induced pluripotent stem cell (iPSC) line generated from immortalized NMR embryonic fibroblasts transduced with a doxycycline-inducible mouse OSKM polycistronic vector. This iPSC line was shown to express pluripotency-associated markers, form embryoid bodies, differentiate in vitro to the derivatives of three germ layers, and exhibit normal kary...
Source: Stem Cell Research - June 21, 2018 Category: Stem Cells Source Type: research

Mitochondrial ROS direct the differentiation of murine pluripotent P19 cells
Publication date: Available online 19 June 2018 Source:Stem Cell Research Author(s): Natalia Pashkovskaia, Uta Gey, Gerhard Rödel ROS are frequently associated with deleterious effects caused by oxidative stress. Despite the harmful effects of non-specific oxidation, ROS also function as signal transduction molecules that regulate various biological processes, including stem cell proliferation and differentiation. Here we show that mitochondrial ROS level determines cell fate during differentiation of the pluripotent stem cell line P19. As stem cells in general, P19 cells are characterized by a low respiration activi...
Source: Stem Cell Research - June 20, 2018 Category: Stem Cells Source Type: research

Establishment of a human induced stem cell line (FUi002-A) from Dravet syndrome patient carrying heterozygous R1525X mutation in SCN1A gene
In this study, human induced pluripotent stem cell (hiPSC) line FUi002-A was generated from skin fibroblasts obtained from a clinically diagnosed 26-year-old male DS patient with the R1525X variant of the SCN1A gene. Skin fibroblasts were reprogrammed using OriP/EBNA-1 based episomal plasmids expressing reprogramming factors expressing OCT4, SOX2, KLF-4, L-MYC, LIN28, and p53 shRNA. The transgene-free FUi002-A showed pluripotency, three germ layer differentiation capacity in vitro, and a normal karyotype. The resulting hiPSCs were heterozygous for the mutation in the SCN1A gene. (Source: Stem Cell Research)
Source: Stem Cell Research - June 20, 2018 Category: Stem Cells Source Type: research

Generation of the Rubinstein-Taybi syndrome type 2 patient-derived induced pluripotent stem cell line (IAIi001-A) carrying the EP300 exon 23 stop mutation c.3829A   & gt;  T, p.(Lys1277*)
Publication date: Available online 18 June 2018 Source:Stem Cell Research Author(s): Valentina Alari, Silvia Russo, Davide Rovina, Aoife Gowran, Maria Garzo, Milena Crippa, Laura Mazzanti, Claudia Scalera, Ennio Prosperi, Daniela Giardino, Cristina Gervasini, Palma Finelli, Giulio Pompilio, Lidia Larizza Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder characterized by growth retardation, skeletal anomalies and intellectual disability, caused by heterozygous mutation in either the CREBBP (RSTS1) or EP300 (RSTS2) genes. We generated an induced pluripotent stem cell line from an RSTS2 patient's blood mononu...
Source: Stem Cell Research - June 19, 2018 Category: Stem Cells Source Type: research

NEK1 loss-of-function mutation induces DNA damage accumulation in ALS patient-derived motoneurons
Publication date: Available online 12 June 2018 Source:Stem Cell Research Author(s): Julia Higelin, Alberto Catanese, Lena Luisa Semelink-Sedlacek, Sertap Oeztuerk, Anne-Kathrin Lutz, Julia Bausinger, Gotthold Barbi, Günter Speit, Peter M. Andersen, Albert C. Ludolph, Maria Demestre, Tobias M. Boeckers Mutations in genes coding for proteins involved in DNA damage response (DDR) and repair, such as C9orf72 and FUS (Fused in Sarcoma), are associated with neurodegenerative diseases and lead to amyotrophic lateral sclerosis (ALS). Heterozygous loss-of-function mutations in NEK1 (NIMA-related kinase 1) have also been rece...
Source: Stem Cell Research - June 13, 2018 Category: Stem Cells Source Type: research

Generation of an induced pluripotent stem cell line from a patient with spinocerebellar ataxia type 3 (SCA3): HIHCNi002-A
Publication date: Available online 11 June 2018 Source:Stem Cell Research Author(s): Stefanie Nicole Hayer, Yvonne Schelling, Jeannette Huebener-Schmid, Jonasz Jeremiasz Weber, Stefan Hauser, Ludger Schöls A skin biopsy of a patient with spinocerebellar ataxia type 3 (SCA3, also known as Machado-Joseph disease (MJD)) caused by a CAG trinucleotide repeat expansion in the ATXN3 gene, was used to generate an induced pluripotent stem cell line, HIHCNi002-A (iPSC-SCA3). Skin fibroblasts were reprogrammed using episomal plasmids carrying hOCT4, hSOX2, hKLF4, hL-MYC, and hLIN28. The iPSC-SCA3 line exhibits chromosomal stabi...
Source: Stem Cell Research - June 12, 2018 Category: Stem Cells Source Type: research

PDK1 regulates definitive HSCs via the FOXO pathway during murine fetal liver hematopoiesis
Publication date: Available online 11 June 2018 Source:Stem Cell Research Author(s): Weili Wang, Xiaolu Sun, Tianyuan Hu, Le Wang, Shuxu Dong, Jie Gu, Yanjing Chu, Xiaomin Wang, Yanhan Li, Yongxin Ru, Tao Cheng, Weiping Yuan PDK1 (phosphoinositide dependent kinase-1) plays an important regulatory role in B cells, T cells and platelets. Less is known about how PDK1 acts in hematopoietic stem cells (HSCs), especially in the fetal liver (FL) during embryonic hematopoiesis, as the FL is the primary fetal hematopoietic organ and the main site of HSC expansion and differentiation. Here, we deleted the PDK1 gene in hematopoietic...
Source: Stem Cell Research - June 12, 2018 Category: Stem Cells Source Type: research

Generation of gene-corrected iPSC line from Parkinson's disease patient iPSC line with alpha-SNCA A53T mutation
Publication date: Available online 9 June 2018 Source:Stem Cell Research Author(s): Seo-Young Lee, SangKyun Jeong, Janghwan Kim, Sun-Ku Chung Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder. PD can result from a mutation of alpha-synuclein (α-SNCA), such as α-SNCA A53T. Using episomal vectors, induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts with the α-SNCA A53T mutation. A huge bacterial artificial chromosome (BAC) harboring the normal α-SNCA gene successfully corrected the α-SNCA A53T-mutant iPSCs. Melting curve analysis f...
Source: Stem Cell Research - June 10, 2018 Category: Stem Cells Source Type: research

Lymphoblast-derived integration-free iPSC line AD-TREM2-3 from a 74  year-old Alzheimer's disease patient expressing the TREM2 p.R47H variant
Publication date: Available online 1 June 2018 Source:Stem Cell Research Author(s): Soraia Martins, Hatice Yigit, Martina Bohndorf, Nina Graffmann, Aurelian Robert Fiszl, Wasco Wruck, Kristel Sleegers, Christine Van Broeckhoven, James Adjaye Human lymphoblast cells from a male diagnosed with Alzheimer's disease (AD) expressing the TREM2 p.R47H variant were used to generate integration-free induced pluripotent stem cells (iPSCs) by over-expressing episomal-based plasmids harbouring OCT4, SOX2, KLF4, LIN28, L-MYC and p53 shRNA. The derived iPSC line – AD-TREM2-3 was defined as pluripotent based on (i) expression of pl...
Source: Stem Cell Research - June 2, 2018 Category: Stem Cells Source Type: research

iPSC-derived neurons of CREBBP- and EP300-mutated Rubinstein-Taybi syndrome patients show morphological alterations and hypoexcitability
Publication date: Available online 30 May 2018 Source:Stem Cell Research Author(s): Valentina Alari, Silvia Russo, Benedetta Terragni, Paola Francesca Ajmone, Alessandra Sironi, Ilaria Catusi, Luciano Calzari, Daniela Concolino, Rosa Marotta, Donatella Milani, Daniela Giardino, Massimo Mantegazza, Cristina Gervasini, Palma Finelli, Lidia Larizza Rubinstein-Taybi syndrome (RSTS) is a rare neurodevelopmental disorder characterized by distinctive facial features, growth retardation, broad thumbs and toes and mild to severe intellectual disability, caused by heterozygous mutations in either CREBBP or EP300 genes, encoding the...
Source: Stem Cell Research - May 31, 2018 Category: Stem Cells Source Type: research

Generation of two isogenic human induced pluripotent stem cell lines from a 15  year-old female patient with MERRF syndrome and A8344G mutation of mitochondrial DNA
Publication date: Available online 28 May 2018 Source:Stem Cell Research Author(s): Shih-Jie Chou, Yu-Ling Ko, Yu-Hsuan Yang, Aliaksandr A. Yarmishyn, Yu-Ting Wu, Chien-Tsun Chen, Hsin-Chen Lee, Yau-Huei Wei, Shih-Hwa Chiou MERRF syndrome is predominantly caused by A8344G mutation in the mitochondrial DNA (mtDNA), affecting MT-TK gene, which impairs the mitochondrial electron transport chain function. Here, we report the generation of two isogenic induced pluripotent stem cell (iPSC) lines, TVGH-iPSC-MRF-Mlow and TVGH-iPSC-MRF-Mhigh, from the skin fibroblasts of a female MERRF patient harboring mtDNA A8344G mutation by us...
Source: Stem Cell Research - May 29, 2018 Category: Stem Cells Source Type: research

Efficient and high yield isolation of myoblasts from skeletal muscle
Publication date: Available online 24 May 2018 Source:Stem Cell Research Author(s): Aref Shahini, Kalyan Vydiam, Debanik Choudhury, Nika Rajabian, Thy Nguyen, Pedro Lei, Stelios T. Andreadis Skeletal muscle (SkM) regeneration relies on the activity of myogenic progenitors that reside beneath the basal lamina of myofibers. Here, we describe a protocol for the isolation of the SkM progenitors from young and old mice by exploiting their outgrowth potential from SkM explants on matrigel coated dishes in the presence of high serum, chicken embryo extract and basic fibroblast growth factor. Compared to other protocols, this met...
Source: Stem Cell Research - May 25, 2018 Category: Stem Cells Source Type: research

Inverse agonism of retinoic acid receptors directs epiblast cells into the paraxial mesoderm lineage
Publication date: Available online 22 May 2018 Source:Stem Cell Research Author(s): Ryan P. Russell, Yu Fu, Yaling Liu, Peter Maye We have investigated the differentiation of paraxial mesoderm from mouse embryonic stem cells utilizing a Tbx6-EYFP/Brachyury (T)- Cherry dual reporter system. Differentiation from the mouse ESC state directly into mesoderm via Wnt pathway activation was low, but augmented by treatment with AGN193109, a pan-retinoic acid receptor inverse agonist. After five days of differentiation, T+ cells increased from 12.2% to 18.8%, Tbx6+ cells increased from 5.8% to 12.7%, and T+/Tbx6+ cells increased fr...
Source: Stem Cell Research - May 23, 2018 Category: Stem Cells Source Type: research

Chondrogenic differentiation in vitro of hiPSCs activates pathways engaged in limb development
Publication date: July 2018 Source:Stem Cell Research, Volume 30 Author(s): Ewelina Stelcer, Katarzyna Kulcenty, Marcin Rucinski, Karol Jopek, Magdalena Richter, Tomasz Trzeciak, Wiktoria Maria SuchorskaGraphical abstract (Source: Stem Cell Research)
Source: Stem Cell Research - May 23, 2018 Category: Stem Cells Source Type: research

Derivation of an induced pluripotent stem cell line (MUSIi004-A) from dermal fibroblasts of a 48-year-old spinocerebellar ataxia type 3 patient
Publication date: Available online 21 May 2018 Source:Stem Cell Research Author(s): Alisa Ritthaphai, Methichit Wattanapanitch, Manop Pithukpakorn, Worapa Heepchantree, Rungtip Soi-ampornkul, Panchalee Mahaisavariya, Daranporn Triwongwaranat, Kovit Pattanapanyasat, Chinnavuth Vatanashevanopakorn Dermal fibroblasts were obtained from a 48-year-old female patient with spinocerebellar ataxia type 3 (SCA3). Fibroblasts were reprogrammed by nucleofection with episomal plasmids, carrying L-MYC, LIN28, OCT4, SOX2, KLF4, EBNA-1 and shRNA against p53. The SCA3 patient-specific iPSC line, MUSIi004-A, was characterized by immunofluo...
Source: Stem Cell Research - May 22, 2018 Category: Stem Cells Source Type: research

Generation of a human CDX2 knock-in reporter iPSC line (MHHi007-A-1) to model human trophoblast differentiation
Publication date: Available online 19 May 2018 Source:Stem Cell Research Author(s): Svitlana Malysheva, Stephanie Wunderlich, Alexandra Haase, Gudrun Göhring, Ulrich Martin, Sylvia Merkert Caudal-type homeobox 2 (CDX2) transcription factor is an important marker for early trophoblast lineages and intestinal epithelium. Due to its nuclear expression the immunostaining and sorting of viable CDX2pos cells is not possible. In this paper we report the generation and describe key characteristics of a CDX2Venus knock-in reporter hiPSC-cell line (MHHi007-A-1) which can serve as a human in vitro tool to study human trophoblas...
Source: Stem Cell Research - May 20, 2018 Category: Stem Cells Source Type: research

Induced pluripotent stem cells derived from a schizophrenia patient with ASTN2 deletion
Publication date: Available online 19 May 2018 Source:Stem Cell Research Author(s): Yuko Arioka, Itaru Kushima, Hisako Kubo, Daisuke Mori, Norio Ozaki Astrotactin-2, encoded by ASTN2, is implicated in neuronal migration. Although genetic studies of schizophrenia (SCZ) patients have suggested that exonic deletions of ASTN2 are associated with neurodevelopmental and psychiatric disorders, their biological significance remains unclear. Herein, we generated human induced pluripotent stem cells (iPSCs) from a SCZ patient with an exonic deletion of ASTN2. The generated iPSCs carried ASTN2 deletion and showed typical iPSC morpho...
Source: Stem Cell Research - May 19, 2018 Category: Stem Cells Source Type: research

Generation of a human induced pluripotent stem cell line from a patient with a rare A673T variant in amyloid precursor protein gene that reduces the risk for Alzheimer's disease
Publication date: Available online 19 May 2018 Source:Stem Cell Research Author(s): Šárka Lehtonen, Ida Höytyläinen, Jenni Voutilainen, Tuuli-Maria Sonninen, Johanna Kuusisto, Markku Laakso, Riikka H. Hämäläinen, Minna Oksanen, Jari Koistinaho An amyloid precursor protein (APP) A673T mutation was found to be protective against Alzheimer's disease (AD) and cognitive decline in the Icelandic population and to associate with decreased levels of plasma β-amyloid in a Finnish population-based cohort. Human fibroblasts from a Finnish male individual carrying the protective mutation we...
Source: Stem Cell Research - May 19, 2018 Category: Stem Cells Source Type: research

Induction of quiescence (G0) in bone marrow stromal stem cells enhances their stem cell characteristics
Publication date: Available online 17 May 2018 Source:Stem Cell Research Author(s): Mohammad Rumman, Abhijit Majumder, Linda Harkness, Balu Venugopal, M.B. Vinay, Malini S. Pillai, Moustapha Kassem, Jyotsna Dhawan Several studies have suggested that bone marrow stromal steam cells (BMSC) exist in a quiescent state (G0) within the in vivo niche; however, an explicit analysis of the biology of G0 state-BMSC has not been reported. We hypothesized that induction of G0 in BMSC might enhance their stem cell properties. Thus, we induced quiescence in BMSC in vitro by (a) suspension culture in a viscous medium or (b) culture on s...
Source: Stem Cell Research - May 18, 2018 Category: Stem Cells Source Type: research

Motor neuron differentiation of iPSCs obtained from peripheral blood of a mutant TARDBP ALS patient
In conclusion, we here demonstrated for the first time that human TARDBP mutated MNs can be successfully obtained exploiting the reprogramming and differentiation ability of peripheral blood cells, an easily accessible source from any patient. (Source: Stem Cell Research)
Source: Stem Cell Research - May 18, 2018 Category: Stem Cells Source Type: research

Isolation of primitive mouse extraembryonic endoderm (pXEN) stem cell lines
Publication date: Available online 18 May 2018 Source:Stem Cell Research Author(s): Yixiang Zhong, Taewoong Choi, Minjae Kim, Kyoung Hwa Jung, Young Gyu Chai, Bert Binas Mouse blastocysts contain the committed precursors of the extraembryonic endoderm (ExEn), which express the key transcription factor Oct4, depend on LIF/LIF-like factor-driven Jak/Stat signaling, and initially exhibit lineage plasticity. Previously described rat blastocyst-derived ExEn precursor-like cell lines (XENP cells/HypoSCs) also show these features, but equivalent mouse blastocyst-derived cell lines are lacking. We now present mouse blastocyst-der...
Source: Stem Cell Research - May 18, 2018 Category: Stem Cells Source Type: research

Establishment of an integration-free induced pluripotent stem cell line (MUSIi005-A) from exfoliated renal epithelial cells
Publication date: Available online 10 May 2018 Source:Stem Cell Research Author(s): Bootsakorn Boonkaew, Weeradee Thummavichit, Ratchapong Netsrithong, Chinnavuth Vatanashevanopakorn, Kovit Pattanapanyasat, Methichit Wattanapanitch Human induced pluripotent stem cells (iPSCs) were generated from exfoliated renal epithelial cells isolated from a urine sample of a 31-year-old healthy woman. Epithelial cells were characterized for the expression of E-cadherin and reprogrammed using non-integrating Sendai viral vectors. The urine-derived iPSC line (designated as MUSIi005-A) was karyotypically normal, expressed pluripotent mar...
Source: Stem Cell Research - May 17, 2018 Category: Stem Cells Source Type: research

Generation of integration-free induced pluripotent stem cells from a patient with spina bifida
Publication date: Available online 17 May 2018 Source:Stem Cell Research Author(s): Hongran Wang, Shuying Zhao, Richard H. Finnell, Timothy George, Austin J. Cooney A skin biopsy was obtained from a 14-year-old female patient with a history of Myelomeningocele. Dermal fibroblasts were isolated and reprogrammed with Sendai virus (SeV) vectors encoding OCT3/4, SOX2, KLF4, and c-MYC. The generated induced Pluripotent Stem Cell (iPSC) clones NTDi4_09A were free of genomically integrated reprogramming genes, had a stable normal karyotype and expressed pluripotency markers. The iPSCs formed teratomas in mice, which were differe...
Source: Stem Cell Research - May 17, 2018 Category: Stem Cells Source Type: research

Metabolic plasticity during transition to na ïve-like pluripotency in canine embryo-derived stem cells
Publication date: July 2018 Source:Stem Cell Research, Volume 30 Author(s): I.C. Tobias, R.R. Isaac, J.G. Dierolf, R. Khazaee, R.C. Cumming, D.H. Betts Pluripotent stem cells (PSCs) have been described in naïve or primed pluripotent states. Domestic dogs are useful translational models in regenerative medicine, but their embryonic stem cells (cESCs) remain narrowly investigated. Primed-like cESCs expanded in the presence of leukemia inhibitory factor and fibroblast growth factor 2 (LIF-FGF2) acquire features of naïve pluripotency when exposed to chemical inhibitors and LIF (2iL). However, proliferation of cESCs ...
Source: Stem Cell Research - May 17, 2018 Category: Stem Cells Source Type: research

Computer simulation of neutral drift among limbal epithelial stem cells of mosaic mice
In this study we used computer simulations to show that these results could also be explained by stochastic replacement of LESCs by neighbouring LESCs, leading to neutral drift of LESC populations. This was shown to reduce the number of coherent clones of LESCs and hence would coarsen the mosaic pattern in the corneal epithelium without reducing the absolute number of LESCs. Simulations also showed that corrected stripe numbers declined more slowly when LESCs were grouped, non-randomly and that mosaicism was rarely lost unless simulated LESC numbers were unrealistically low. Possible reasons why age-related changes differ ...
Source: Stem Cell Research - May 14, 2018 Category: Stem Cells Source Type: research

Developing two reference control samples for the Indian population
Publication date: Available online 12 May 2018 Source:Stem Cell Research Author(s): Shruti Iyer, Priyanka Bhatia, Mahendra Rao, Odity Mukherjee Human induced Pluripotent Stem Cells (HiPSCs) have immense potential in research and therapeutics. Under the aegis of Department of Biotechnology funded national program entitled, “The Accelerator program for Discovery in Brain Disorders using Stem Cells (ADBS)” we have established a HiPSC biorepository (https://www.ncbs.res.in/adbs/bio-repository) with an objective to study severe mental illness. The repository comprises of HiPSC lines derived from healthy control don...
Source: Stem Cell Research - May 13, 2018 Category: Stem Cells Source Type: research

CD133+ cells derived from skeletal muscles of Duchenne muscular dystrophy patients have a compromised myogenic and muscle regenerative capability
Publication date: Available online 12 May 2018 Source:Stem Cell Research Author(s): Jinhong Meng, Francesco Muntoni, Jennifer Morgan Cell-mediated gene therapy is a possible means to treat muscular dystrophies like Duchenne muscular dystrophy. Autologous patient stem cells can be genetically-corrected and transplanted back into the patient, without causing immunorejection problems. Regenerated muscle fibres derived from these cells will express the missing dystrophin protein, thus improving muscle function. CD133+ cells derived from normal human skeletal muscle contribute to regenerated muscle fibres and form muscle stem ...
Source: Stem Cell Research - May 13, 2018 Category: Stem Cells Source Type: research

Generation of an induced pluripotent stem cell line from a patient with non-syndromic CLN3-associated retinal degeneration and a coisogenic control line
We report the generation of the human iPSC line LEIi004-A from a patient with late-onset non-syndromic retinitis pigmentosa caused by compound heterozygous mutations in the CLN3 gene. Reprogramming of primary dermal fibroblasts was performed using episomal plasmids containing OCT4, SOX2, KLF4, L-MYC, LIN28, shRNA for p53 and mir302/367 microRNA. To create a coisogenic control line, one CLN3 variant was corrected in the patient-iPSC using CRISPR/Cas9 gene editing to generate the iPSC line LEIi004-A-1. (Source: Stem Cell Research)
Source: Stem Cell Research - May 2, 2018 Category: Stem Cells Source Type: research

Feedback control of pluripotency in embryonic stem cells: Signaling, transcription and epigenetics
Publication date: May 2018 Source:Stem Cell Research, Volume 29 Author(s): Dmitri Papatsenko, Avinash Waghray, Ihor R. Lemischka Embryonic stem cells (ESCs) can proliferate and self-renew, maintaining their pluripotency status in vitro for a long period of time. Pluripotent states of ESCs in vitro are supported by a network of signaling, transcriptional and epigenetic regulatory interactions known as the pluripotency gene regulatory network (PGRN). Despite extensive investigation of the network, the exact order of regulatory links and many structural features of the network are still missing. Analysis of published data an...
Source: Stem Cell Research - May 2, 2018 Category: Stem Cells Source Type: research

Derivation and characterization of the NIH registry human stem cell line NYSCF101 under defined feeder-free conditions
Publication date: Available online 30 April 2018 Source:Stem Cell Research Author(s): Ana Sevilla, Eliana Forero, Matthew Zimmer, Hector Martinez, Katie Reggio, Daniel Paull, Dieter Egli, Scott Noggle The human embryonic stem cell line NYSCFe002-A was derived from a day 6 blastocyst in feeder-free and antibiotic free conditions. The blastocyst was voluntarily donated for research as surplus after in vitro fertilization treatment following informed consent. The NYSCFe002-A line expresses all the pluripotency markers and has the potential to differentiate into all three germ layers in vitro. The line presents normal karyoty...
Source: Stem Cell Research - May 1, 2018 Category: Stem Cells Source Type: research

Efficient production of erythroid, megakaryocytic and myeloid cells, using single cell-derived iPSC colony differentiation
Publication date: Available online 28 April 2018 Source:Stem Cell Research Author(s): Marten Hansen, Eszter Varga, Cathelijn Aarts, Tatjana Wust, Taco Kuijpers, Marieke von Lindern, Emile van den Akker Hematopoietic differentiation of human induced pluripotent stem cells (iPSCs) provide opportunities not only for fundamental research and disease modelling/drug testing but also for large-scale production of blood effector cells for future clinical application. Although there are multiple ways to differentiate human iPSCs towards hematopoietic lineages, there is a need to develop reproducible and robust protocols. Here we i...
Source: Stem Cell Research - April 28, 2018 Category: Stem Cells Source Type: research

Generation and characterization of a human iPS cell line from a patient-related control to study disease mechanisms associated with DAND5 p.R152H alteration
Publication date: Available online 28 April 2018 Source:Stem Cell Research Author(s): Selin Pars, Fernando Cristo, José M. Inácio, Graça Rosas, Isabel Marques Carreira, Joana Barbosa Melo, Patrícia Mendes, Duarte Saraiva Martins, Luís Pereira de Almeida, José Maio, Rui Anjos, José A. Belo A DAND5-control human iPSC line was generated from the urinary cells of a phenotypically normal donor. Exfoliated renal epithelial (RE) cells were collected and reprogrammed into iPSCs using Sendai virus reprogramming system. The pluripotency, in vitro differentiation potential, karyotype ...
Source: Stem Cell Research - April 28, 2018 Category: Stem Cells Source Type: research

Direct conversion of human pluripotent stem cells into cranial motor neurons using a piggyBac vector
Publication date: Available online 27 April 2018 Source:Stem Cell Research Author(s): Riccardo De Santis, Maria Giovanna Garone, Francesca Pagani, Valeria de Turris, Silvia Di Angelantonio, Alessandro Rosa Human pluripotent stem cells (PSCs) are widely used for in vitro disease modeling. One of the challenges in the field is represented by the ability of converting human PSCs into specific disease-relevant cell types. The nervous system is composed of a wide variety of neuronal types with selective vulnerability in neurodegenerative diseases. This is particularly relevant for motor neuron diseases, in which different moto...
Source: Stem Cell Research - April 27, 2018 Category: Stem Cells Source Type: research

Establishment of a human embryonic stem cell line with homozygous TP53 R248W mutant by TALEN mediated gene editing
Publication date: Available online 27 April 2018 Source:Stem Cell Research Author(s): An Xu, Ruoji Zhou, Jian Tu, Zijun Huo, Dandan Zhu, Donghui Wang, Julian A. Gingold, Helen Mata, Pulivarthi H. Rao, Mo Liu, Alaa M.T. Mohamed, Celine Shuet Lin Kong, Brittany E. Jewell, Weiya Xia, Ruiying Zhao, Mien-Chie Hung, Dung-Fang Lee Genetic mutations in TP53 contribute to multiple human cancers. Here we report the generation of a H1-p53(R248W/R248W) human embryonic stem cell line harboring a homozygous TP53 R248W mutation created by TALEN-mediated precise gene editing. The H1-p53(R248W/R248W) cell line maintains a normal karyotype...
Source: Stem Cell Research - April 27, 2018 Category: Stem Cells Source Type: research

NKX6.1 induced pluripotent stem cell reporter lines for isolation and analysis of functionally relevant neuronal and pancreas populations
Publication date: Available online 23 April 2018 Source:Stem Cell Research Author(s): Shailesh Kumar Gupta, Agata Wesolowska-Andersen, Anna K. Ringgaard, Himjyot Jaiswal, Luyan Song, Benoit Hastoy, Camilla Ingvorsen, Amir Taheri-Ghahfarokhi, Björn Magnusson, Marcello Maresca, Rikke R. Jensen, Nicola L. Beer, Johannes J. Fels, Lars G. Grunnet, Melissa K. Thomas, Anna L. Gloyn, Ryan Hicks, Mark I. McCarthy, Mattias Hansson, Christian Honoré Recent studies have reported significant advances in the differentiation of human pluripotent stem cells to clinically relevant cell types such as the insulin producing beta-...
Source: Stem Cell Research - April 24, 2018 Category: Stem Cells Source Type: research

Blood-derived integration-free iPS cell line UKBi011-A from a diagnosed male Alzheimer's disease patient with APOE ɛ4/ɛ4 genotype
Publication date: Available online 23 April 2018 Source:Stem Cell Research Author(s): Michael Peitz, Tamara Bechler, Catrin Cornelia Thiele, Monika Veltel, Melanie Bloschies, Klaus Fliessbach, Alfredo Ramirez, Oliver Brüstle Alzheimer's disease (AD) is most the frequent neurodegenerative disease, and the APOE ε4 allele is the most prominent risk factor for late-onset AD. Here, we present an iPSC line generated from peripheral blood cells of a male AD patient employing Sendai virus vectors encoding the transcription factors OCT4, SOX2, KLF4 and c-MYC. The characterized iPSC line expresses typical human pluripo...
Source: Stem Cell Research - April 24, 2018 Category: Stem Cells Source Type: research

Derivation and characterization of a UCP1 reporter human ES cell line
This reporter cell line thus presents new opportunities to study human brown fat biology by enabling future work to understand early human brown fat development, perform disease modeling, and facilitate drug screening. (Source: Stem Cell Research)
Source: Stem Cell Research - April 23, 2018 Category: Stem Cells Source Type: research

Generation of the induced pluripotent stem cell line CSSi006-A (3681) from a patient affected by advanced-stage Juvenile Onset Huntington's Disease
Publication date: Available online 21 April 2018 Source:Stem Cell Research Author(s): Giovannina Rotundo, Eris Bidollari, Daniela Ferrari, Iolanda Spasari, Laura Bernardini, Federica Consoli, Alessandro De Luca, Iolanda Santimone, Giuseppe Lamorte, Simone Migliore, Ferdinando Squitieri, Angelo Luigi Vescovi, Jessica Rosati Juvenile Onset Huntington's Disease (JOHD) is a rare variant of HD withage of onset ≤20 years, accounting for 3–10% of all HD patients. The rarity occurrence of JOHD cases, who severely progress towards mental and physical disability with atypical clinical manifestations compared to classical...
Source: Stem Cell Research - April 22, 2018 Category: Stem Cells Source Type: research

Spermatogonial stem cells and spermatogenesis in mice, monkeys and men
Publication date: Available online 21 April 2018 Source:Stem Cell Research Author(s): Adetunji P. Fayomi, Kyle E. Orwig Continuous spermatogenesis in post-pubertal mammals is dependent on spermatogonial stem cells (SSCs), which balance self-renewing divisions that maintain stem cell pool with differentiating divisions that sustain continuous sperm production. Rodent stem and progenitor spermatogonia are described by their clonal arrangement in the seminiferous epithelium (e.g., Asingle, Apaired or Aaligned spermatogonia), molecular markers (e.g., ID4, GFRA1, PLZF, SALL4 and others) and most importantly by their biological...
Source: Stem Cell Research - April 22, 2018 Category: Stem Cells Source Type: research

Generation of an integration-free iPSC line (CSCRi005-A) from erythroid progenitor cells of a healthy Indian male individual
We describe here an iPSC line generated using such conditions, which expressed all the pluripotency markers, retained normal karyotype and exhibited the potential for tri-lineage differentiation, both in-vitro and in-vivo. This is the first iPSC line available from a healthy Indian individual for researchers. (Source: Stem Cell Research)
Source: Stem Cell Research - April 14, 2018 Category: Stem Cells Source Type: research

Generation of the human induced pluripotent stem cell (hiPSC) line PSMi003-A from a patient affected by an autosomal recessive form of Long QT Syndrome type 1
Publication date: Available online 6 April 2018 Source:Stem Cell Research Author(s): Manuela Mura, Monia Ginevrino, Rita Zappatore, Federica Pisano, Marina Boni, Silvia Castelletti, Lia Crotti, Enza Maria Valente, Peter J. Schwartz, Massimiliano Gnecchi We generated human induced pluripotent stem cells (hiPSCs) from dermal fibroblasts of a 51 years old female patient homozygous for the mutation c.535 G>A p.G179S on the KCNQ1 gene, causing a severe form of autosomal recessive Long QT Syndrome type 1 (AR-LQT1), not associated with deafness. The hiPSCs, generated using four retroviruses each encoding for a reprogram...
Source: Stem Cell Research - April 14, 2018 Category: Stem Cells Source Type: research

Generation of the human induced pluripotent stem cell (hiPSC) line PSMi002-A from a patient affected by the Jervell and Lange-Nielsen syndrome and carrier of two compound heterozygous mutations on the KCNQ1 gene
We report the generation of human induced pluripotent stem cells (hiPSCs) from dermal fibroblasts of a female patient carrier of the two compound heterozygous mutations c.568 C>T p.R190W (maternal allele), and c.1781 G>A p.R594Q (paternal allele) on the KCNQ1 gene, causing Jervell and Lange-Nielsen Syndrome (JLNS). To obtain hiPSCs, we used the classical approach of the four retroviruses each encoding for a reprogramming factor OCT4, SOX2, KLF4, cMYC. The obtained hiPSC clones display pluripotent stem cell characteristics, and differentiate into spontaneously beating cardiomyocytes (hiPSC-CMs). (Source: Stem Cell Research)
Source: Stem Cell Research - April 14, 2018 Category: Stem Cells Source Type: research