Human Cortical Organoids Expose a Differential Function of GSK3 on Cortical Neurogenesis
Publication date: Available online 10 October 2019Source: Stem Cell ReportsAuthor(s): Alejandro López-Tobón, Carlo Emanuele Villa, Cristina Cheroni, Sebastiano Trattaro, Nicolò Caporale, Paola Conforti, Raffaele Iennaco, Maria Lachgar, Marco Tullio Rigoli, Berta Marcó de la Cruz, Pietro Lo Riso, Erika Tenderini, Flavia Troglio, Marco De Simone, Isabel Liste-Noya, Giuseppe Macino, Massimiliano Pagani, Elena Cattaneo, Giuseppe TestaSummaryThe regulation of the proliferation and polarity of neural progenitors is crucial for the development of the brain cortex. Animal studies have implicated glycoge...
Source: Stem Cell Reports - October 12, 2019 Category: Stem Cells Source Type: research

Viagra Enables Efficient, Single-Day Hematopoietic Stem Cell Mobilization
Publication date: Available online 10 October 2019Source: Stem Cell ReportsAuthor(s): Stephanie Smith-Berdan, Alyssa Bercasio, Smrithi Rajendiran, E. Camilla ForsbergSummaryHematopoietic stem cell (HSC) transplantation is a curative treatment for a variety of blood and immune disorders. Currently available methods to obtain donor HSCs are suboptimal, and the limited supply of donor HSCs hampers the success and availability of HSC transplantation therapies. We recently showed that manipulation of vascular integrity can be employed to induce HSC mobilization from the bone marrow to the blood stream, facilitating non-invasive...
Source: Stem Cell Reports - October 12, 2019 Category: Stem Cells Source Type: research

Interplay between Metabolites and the Epigenome in Regulating Embryonic and Adult Stem Cell Potency and Maintenance
Publication date: 8 October 2019Source: Stem Cell Reports, Volume 13, Issue 4Author(s): Alexandra Harvey, Giuseppina Caretti, Viviana Moresi, Alessandra Renzini, Sergio AdamoThe environment surrounding stem cells has the ability to elicit profound, heritable epigenetic changes orchestrated by multiple epigenetic mechanisms, which can be modulated by the level of specific metabolites. In this review, we highlight the significance of metabolism in regulating stem cell homeostasis, cell state, and differentiation capacity, using metabolic regulation of embryonic and adult muscle stem cells as examples, and cast light on the i...
Source: Stem Cell Reports - October 9, 2019 Category: Stem Cells Source Type: research

Continuous WNT Control Enables Advanced hPSC Cardiac Processing and Prognostic Surface Marker Identification in Chemically Defined Suspension Culture
Publication date: 8 October 2019Source: Stem Cell Reports, Volume 13, Issue 4Author(s): Caroline Halloin, Kristin Schw.e, Wiebke Löbel, Annika Franke, Monika Szepes, Santoshi Biswanath, Stephanie Wunderlich, Sylvia Merkert, Natalie Weber, Felix Osten, Jeanne de la Roche, Felix Polten, Kai Christoph Wollert, Theresia Kraft, Martin Fischer, Ulrich Martin, Ina Gruh, Henning Kempf, Robert Zweigerdt (Source: Stem Cell Reports)
Source: Stem Cell Reports - October 9, 2019 Category: Stem Cells Source Type: research

Stem Cell Modeling of Neuroferritinopathy Reveals Iron as a Determinant of Senescence and Ferroptosis during Neuronal Aging
Publication date: Available online 3 October 2019Source: Stem Cell ReportsAuthor(s): Anna Cozzi, Daniel I. Orellana, Paolo Santambrogio, Alicia Rubio, Cinzia Cancellieri, Serena Giannelli, Maddalena Ripamonti, Stefano Taverna, Giulia Di Lullo, Ermanna Rovida, Maurizio Ferrari, Gian Luca Forni, Chiara Fiorillo, Vania Broccoli, Sonia LeviSummaryNeuroferritinopathy (NF) is a movement disorder caused by alterations in the L-ferritin gene that generate cytosolic free iron. NF is a unique pathophysiological model for determining the direct consequences of cell iron dysregulation. We established lines of induced pluripotent stem ...
Source: Stem Cell Reports - October 5, 2019 Category: Stem Cells Source Type: research

ALDH-Dependent Glycolytic Activation Mediates Stemness and Paclitaxel Resistance in Patient-Derived Spheroid Models of Uterine Endometrial Cancer
Publication date: Available online 26 September 2019Source: Stem Cell ReportsAuthor(s): Yutaro Mori, Kaoru Yamawaki, Tatsuya Ishiguro, Kosuke Yoshihara, Haruka Ueda, Ai Sato, Hirokazu Ohata, Yohko Yoshida, Tohru Minamino, Koji Okamoto, Takayuki EnomotoSummaryUterine endometrial cancer is associated with poor survival outcomes in patients with advanced-stage disease. Here, we developed a three-dimensional cell cultivation method of endometrioid cancer stem-like cells with high aldehyde dehydrogenase (ALDH) activity from clinical specimens. ALDH inhibition synergized with paclitaxel to block cancer proliferation. In the clin...
Source: Stem Cell Reports - September 28, 2019 Category: Stem Cells Source Type: research

Base-Resolution Methylome of Retinal Pigment Epithelial Cells Used in the First Trial of Human Induced Pluripotent Stem Cell-Based Autologous Transplantation
Publication date: Available online 26 September 2019Source: Stem Cell ReportsAuthor(s): Hiromitsu Araki, Fumihito Miura, Akira Watanabe, Chikako Morinaga, Fumiyo Kitaoka, Yuko Kitano, Noriko Sakai, Yumiko Shibata, Motoki Terada, So Goto, Shinya Yamanaka, Masayo Takahashi, Takashi ItoSummaryThe first-in-human trial of induced pluripotent stem cell (iPSC)-based autologous transplantation was successfully performed on a female patient with age-related macular degeneration. Here we delineated the base-resolution methylome of the iPSC-derived retinal pigment epithelium (iRPE) used in this trial. The methylome of iRPE closely re...
Source: Stem Cell Reports - September 28, 2019 Category: Stem Cells Source Type: research

Fatty Acids Enhance the Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells
Publication date: Available online 26 September 2019Source: Stem Cell ReportsAuthor(s): Xiulan Yang, Marita L. Rodriguez, Andrea Leonard, Lihua Sun, Karin A. Fischer, Yuliang Wang, Julia Ritterhoff, Limei Zhao, Stephen C. Kolwicz, Lil Pabon, Hans Reinecke, Nathan J. Sniadecki, Rong Tian, Hannele Ruohola-Baker, Haodong Xu, Charles E. MurrySummaryAlthough human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have emerged as a novel platform for heart regeneration, disease modeling, and drug screening, their immaturity significantly hinders their application. A hallmark of postnatal cardiomyocyte maturation is the met...
Source: Stem Cell Reports - September 28, 2019 Category: Stem Cells Source Type: research

H3K18ac Primes Mesendodermal Differentiation upon Nodal Signaling
Publication date: Available online 26 September 2019Source: Stem Cell ReportsAuthor(s): Maoguo Luo, Jianbo Bai, Bofeng Liu, Peiqiang Yan, Feifei Zuo, Hongyao Sun, Ye Sun, Xuanhao Xu, Zhihong Song, Yang Yang, Joan Massagué, Xun Lan, Zhi Lu, Ye-Guang Chen, Haiteng Deng, Wei Xie, Qiaoran XiSummaryCellular responses to transforming growth factor β (TGF-β) depend on cell context. Here, we explored how TGF-β/nodal signaling crosstalks with the epigenome to promote mesendodermal differentiation. We find that expression of a group of mesendodermal genes depends on both TRIM33 and nodal signaling in embryoid b...
Source: Stem Cell Reports - September 28, 2019 Category: Stem Cells Source Type: research

Lineage Tracing and Cell Potential of Postnatal Single Progenitor Cells In Vivo
Publication date: Available online 19 September 2019Source: Stem Cell ReportsAuthor(s): María Figueres-Oñate, Mario Sánchez-Villalón, Rebeca Sánchez-González, Laura López-MascaraqueSummaryUnderstanding the contribution of adult neural progenitor cells (NPCs) and their lineage potential is a great challenge in neuroscience. To reveal progenitor diversity and cell-lineage relationships of postnatal NPCs in the subventricular zone (SVZ), we performed in vivo lineage-tracing genetic analysis using the UbC-StarTrack. We determined the progeny of single SVZ-NPCs, the number o...
Source: Stem Cell Reports - September 20, 2019 Category: Stem Cells Source Type: research

Single-Cell RNA Sequencing of hESC-Derived 3D Retinal Organoids Reveals Novel Genes Regulating RPC Commitment in Early Human Retinogenesis
In this study, by performing single-cell RNA sequencing of cells isolated from human embryonic stem cell (hESC)-derived 3D retinal organoids, we successfully deconstructed the temporal progression of RPCs during early human retinogenesis. We identified two distinctive subtypes of RPCs with unique molecular profiles, namely multipotent RPCs and neurogenic RPCs. We found that genes related to the Notch and Wnt signaling pathways, as well as chromatin remodeling, were dynamically regulated during RPC commitment. Interestingly, our analysis identified that CCND1, a G1-phase cell-cycle regulator, was coexpressed with ASCL1 in a...
Source: Stem Cell Reports - September 20, 2019 Category: Stem Cells Source Type: research

Pathological Progression Induced by the Frontotemporal Dementia-Associated R406W Tau Mutation in Patient-Derived iPSCs
In this study, we established patient-derived induced pluripotent stem cell (iPSC) models to investigate the disease pathology induced by the R406W mutation. We generated iPSCs from patients and established isogenic lines using CRISPR/Cas9. The iPSCs were induced into cerebral organoids, which were dissociated into cortical neurons with high purity. In this neuronal culture, the mutant tau protein exhibited reduced phosphorylation levels and was increasingly fragmented by calpain. Furthermore, the mutant tau protein was mislocalized and the axons of the patient-derived neurons displayed morphological and functional abnorma...
Source: Stem Cell Reports - September 20, 2019 Category: Stem Cells Source Type: research

Targeted Repair of p47-CGD in iPSCs by CRISPR/Cas9: Functional Correction without Cleavage in the Highly Homologous Pseudogenes
Publication date: Available online 19 September 2019Source: Stem Cell ReportsAuthor(s): Denise Klatt, Erica Cheng, Friederike Philipp, Anton Selich, Julia Dahlke, Reinhold E. Schmidt, Juliane W. Schott, Hildegard Büning, Dirk Hoffmann, Adrian J. Thrasher, Axel SchambachSummaryMutations in the NADPH oxidase, which is crucial for the respiratory burst in phagocytes, result in chronic granulomatous disease (CGD). The only curative treatment option for CGD patients, who suffer from severe infections, is allogeneic bone marrow transplantation. Over 90% of patients with mutations in the p47phox subunit of the oxidase comple...
Source: Stem Cell Reports - September 20, 2019 Category: Stem Cells Source Type: research

Lgr5 and Col22a1 Mark Progenitor Cells in the Lineage toward Juvenile Articular Chondrocytes
Publication date: Available online 12 September 2019Source: Stem Cell ReportsAuthor(s): Chen Feng, Wilson Cheuk Wing Chan, Yan Lam, Xue Wang, Peikai Chen, Ben Niu, Vivian Chor Wing Ng, Jia Chi Yeo, Sigmar Stricker, Kathryn Song Eng Cheah, Manuel Koch, Stefan Mundlos, Huck Hui Ng, Danny ChanSummaryThe synovial joint forms from a pool of progenitor cells in the future region of the joint, the interzone. Expression of Gdf5 and Wnt9a has been used to mark the earliest cellular processes in the formation of the interzone and the progenitor cells. However, lineage specification and progression toward the different tissues o...
Source: Stem Cell Reports - September 14, 2019 Category: Stem Cells Source Type: research

PSEN1ΔE9, APPswe, and APOE4 Confer Disparate Phenotypes in Human iPSC-Derived Microglia
We present a physiologically relevant high-yield protocol for producing iMGLs from induced pluripotent stem cells. Differentiation is directed with small molecules through primitive erythromyeloid progenitors to re-create microglial ontogeny from yolk sac. The iMGLs express microglial signature genes and respond to ADP with intracellular Ca2+ release distinguishing them from macrophages. Using 16 iPSC lines from healthy donors, AD patients and isogenic controls, we reveal that the APOE4 genotype has a profound impact on several aspects of microglial functionality, whereas PSEN1ΔE9 and APPswe mutations trigg...
Source: Stem Cell Reports - September 14, 2019 Category: Stem Cells Source Type: research

Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling
Publication date: Available online 12 September 2019Source: Stem Cell ReportsAuthor(s): Soheil Akbari, Gülben Gürhan Sevinç, Nevin Ersoy, Onur Basak, Kubra Kaplan, Kenan Sevinç, Erkin Ozel, Berke Sengun, Eray Enustun, Burcu Ozcimen, Alper Bagriyanik, Nur Arslan, Tamer Tevfik Önder, Esra ErdalSummaryOrganoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and charact...
Source: Stem Cell Reports - September 14, 2019 Category: Stem Cells Source Type: research

A Chemically Defined Feeder-free System for the Establishment and Maintenance of the Human Naive Pluripotent State
Publication date: Available online 12 September 2019Source: Stem Cell ReportsAuthor(s): Iwona Szczerbinska, Kevin Andrew Uy Gonzales, Engin Cukuroglu, Muhammad Nadzim Bin Ramli, Bertha Pei Ge Lee, Cheng Peow Tan, Cheng Kit Wong, Giulia Irene Rancati, Hongqing Liang, Jonathan Göke, Huck-Hui Ng, Yun-Shen ChanSummaryThe distinct states of pluripotency in the pre- and post-implantation embryo can be captured in vitro as naive and primed pluripotent stem cell cultures, respectively. The study and application of the naive state remains hampered, particularly in humans, partially due to current culture protocols relying...
Source: Stem Cell Reports - September 14, 2019 Category: Stem Cells Source Type: research

Building Blastocysts from Stem Cells
Publication date: 10 September 2019Source: Stem Cell Reports, Volume 13, Issue 3Author(s): Maayan Pour, Iftach NachmanThe blastocyst stage and the subsequent implantation are critical for a successful pregnancy, yet are challenging to study in vivo. In this issue of Stem Cell Reports, Kime et al. (2019) describe a novel way to generate blastocyst-like structures only from pluripotent stem cells. These structures mimic several aspects of the early embryo, offering a new promising tool to study this stage. (Source: Stem Cell Reports)
Source: Stem Cell Reports - September 11, 2019 Category: Stem Cells Source Type: research

The Ethics of Cerebral Organoid Research: Being Conscious of Consciousness
Publication date: 10 September 2019Source: Stem Cell Reports, Volume 13, Issue 3Author(s): Tsutomu Sawai, Hideya Sakaguchi, Elizabeth Thomas, Jun Takahashi, Misao FujitaRecently, the use of three-dimensional neural tissues cultured in vitro and called "cerebral organoids" has advanced recapitulation of neural development and disease modeling studies. Along with such advances, cerebral organoid research, and associated concerns call for the elucidation of two points: (1) how cerebral organoid research is currently progressing and the future directions it is likely to take, especially in functional a...
Source: Stem Cell Reports - September 11, 2019 Category: Stem Cells Source Type: research

Derivation of Brain Capillary-like Endothelial Cells from Human Pluripotent Stem Cell-Derived Endothelial Progenitor Cells
Publication date: Available online 5 September 2019Source: Stem Cell ReportsAuthor(s): Catarina Praça, Susana C. Rosa, Emmanuel Sevin, Romeo Cecchelli, Marie-Pierre Dehouck, Lino S. FerreiraSummaryThe derivation of human brain capillary endothelial cells is of utmost importance for drug discovery programs focusing on diseases of the central nervous system. Here, we describe a two-step differentiation protocol to derive brain capillary-like endothelial cells from human pluripotent stem cells. The cells were initially differentiated into endothelial progenitor cells followed by specification into a brain capillary-lik...
Source: Stem Cell Reports - September 6, 2019 Category: Stem Cells Source Type: research

Dynamical Electrical Complexity Is Reduced during Neuronal Differentiation in Autism Spectrum Disorder
Publication date: Available online 29 August 2019Source: Stem Cell ReportsAuthor(s): Debha N. Amatya, Sara B. Linker, Ana P.D. Mendes, Renata Santos, Galina Erikson, Maxim N. Shokhirev, Yuansheng Zhou, Tatyana Sharpee, Fred H. Gage, Maria C. Marchetto, Yeni KimSummaryNeuronal activity can be modeled as a nonlinear dynamical system to yield measures of neuronal state and dysfunction. The electrical recordings of stem cell-derived neurons from individuals with autism spectrum disorder (ASD) and controls were analyzed using minimum embedding dimension (MED) analysis to characterize their dynamical complexity. MED analysis rev...
Source: Stem Cell Reports - August 31, 2019 Category: Stem Cells Source Type: research

CTIP2-Regulated Reduction in PKA-Dependent DARPP32 Phosphorylation in Human Medium Spiny Neurons: Implications for Huntington Disease
This study therefore establishes an essential role for CTIP2 in human MSN homeostasis and provides mechanistic and potential therapeutic insight into striatal neurodegeneration. (Source: Stem Cell Reports)
Source: Stem Cell Reports - August 24, 2019 Category: Stem Cells Source Type: research

Generation of a Purified iPSC-Derived Smooth Muscle-like Population for Cell Sheet Engineering
Publication date: Available online 15 August 2019Source: Stem Cell ReportsAuthor(s): George Kwong, Hector A. Marquez, Chian Yang, Joyce Y. Wong, Darrell N. KottonSummaryInduced pluripotent stem cells (iPSCs) provide a potential source for the derivation of smooth muscle cells (SMCs); however, current approaches are limited by the production of heterogeneous cell types and a paucity of tools or markers for tracking and purifying candidate SMCs. Here, we develop murine and human iPSC lines carrying fluorochrome reporters (Acta2hrGFP and ACTA2eGFP, respectively) that identify Acta2+/ACTA2+ cells as they emerge in vitro i...
Source: Stem Cell Reports - August 16, 2019 Category: Stem Cells Source Type: research

Estrogen Receptor β2 Oversees Germ Cell Maintenance and Gonadal Sex Differentiation in Medaka, Oryzias latipes
This study is expected improve our understanding of germ cell maintenance and sex spectrum, and hence open new avenues for reproductive disorder management. (Source: Stem Cell Reports)
Source: Stem Cell Reports - August 14, 2019 Category: Stem Cells Source Type: research

Transcriptional Profiling of Stem Cells: Moving from Descriptive to Predictive Paradigms
Publication date: 13 August 2019Source: Stem Cell Reports, Volume 13, Issue 2Author(s): Christine A. Wells, Jarny ChoiTranscriptional profiling is a powerful tool commonly used to benchmark stem cells and their differentiated progeny. As the wealth of stem cell data builds in public repositories, we highlight common data traps, and review approaches to combine and mine this data for new cell classification and cell prediction tools. We touch on future trends for stem cell profiling, such as single-cell profiling, long-read sequencing, and improved methods for measuring molecular modifications on chromatin and RNA that brin...
Source: Stem Cell Reports - August 14, 2019 Category: Stem Cells Source Type: research

Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes
Publication date: 13 August 2019Source: Stem Cell Reports, Volume 13, Issue 2Author(s): An Verheyen, Annick Diels, Joke Reumers, Kirsten Van Hoorde, Ilse Van den Wyngaert, Constantin van Outryve d’Ydewalle, An De Bondt, Jacobine Kuijlaars, Louis De Muynck, Ronald De Hoogt, Alexis Bretteville, Steffen Jaensch, Arjan Buist, Alfredo Cabrera-Socorro, Selina Wray, Andreas Ebneth, Peter Roevens, Ines Royaux, Pieter J. Peeters (Source: Stem Cell Reports)
Source: Stem Cell Reports - August 14, 2019 Category: Stem Cells Source Type: research

The REGγ-Proteasome Regulates Spermatogenesis Partially by P53-PLZF Signaling
Publication date: Available online 8 August 2019Source: Stem Cell ReportsAuthor(s): Xiao Gao, Hui Chen, Jian Liu, Shihui Shen, Qingwei Wang, Tracy M. Clement, Brian J. Deskin, Caiyu Chen, Dengpan Zhao, Lu Wang, Linjie Guo, Xueqing Ma, Bianhong Zhang, Yunfei Xu, Xiaotao Li, Lei LiSummaryDevelopment of spermatogonia and spermatocytes are the critical steps of spermatogenesis, impacting on male fertility. Investigation of the related regulators benefits the understanding of male reproduction. The proteasome system has been reported to regulate spermatogenesis, but the mechanisms and key contributing factors in vivo are p...
Source: Stem Cell Reports - August 9, 2019 Category: Stem Cells Source Type: research

GATA2 Promotes Hematopoietic Development and Represses Cardiac Differentiation of Human Mesoderm
Publication date: Available online 8 August 2019Source: Stem Cell ReportsAuthor(s): Julio Castaño, Sergi Aranda, Clara Bueno, Fernando J. Calero-Nieto, Eva Mejia-Ramirez, Jose Luis Mosquera, Enrique Blanco, Xiaonan Wang, Cristina Prieto, Lorea Zabaleta, Elisabetta Mereu, Meritxell Rovira, Senda Jiménez-Delgado, Daniel R. Matson, Holger Heyn, Emery H. Bresnick, Berthold Göttgens, Luciano Di Croce, Pablo Menendez, Angel RayaSummaryIn vertebrates, GATA2 is a master regulator of hematopoiesis and is expressed throughout embryo development and in adult life. Although the essential role of GATA2 in mouse hemat...
Source: Stem Cell Reports - August 9, 2019 Category: Stem Cells Source Type: research

Induced 2C Expression and Implantation-Competent Blastocyst-like Cysts from Primed Pluripotent Stem Cells
Publication date: Available online 8 August 2019Source: Stem Cell ReportsAuthor(s): Cody Kime, Hiroshi Kiyonari, Satoshi Ohtsuka, Eiko Kohbayashi, Michio Asahi, Shinya Yamanaka, Masayo Takahashi, Kiichiro TomodaSummarySoon after fertilization, the few totipotent cells of mammalian embryos diverge to form a structure called the blastocyst (BC). Although numerous cell types, including germ cells and extended-pluripotency stem cells, have been developed from pluripotent stem cells (PSCs) in vitro, generating functional BCs only from PSCs remains elusive. Here, we describe induced self-organizing 3D BC-like cysts (iBLCs) ...
Source: Stem Cell Reports - August 9, 2019 Category: Stem Cells Source Type: research

Simple and Robust Differentiation of Human Pluripotent Stem Cells toward Chondrocytes by Two Small-Molecule Compounds
Publication date: Available online 8 August 2019Source: Stem Cell ReportsAuthor(s): Manabu Kawata, Daisuke Mori, Kosuke Kanke, Hironori Hojo, Shinsuke Ohba, Ung-il Chung, Fumiko Yano, Hideki Masaki, Makoto Otsu, Hiromitsu Nakauchi, Sakae Tanaka, Taku SaitoSummaryA simple induction protocol to differentiate chondrocytes from pluripotent stem cells (PSCs) using small-molecule compounds is beneficial for cartilage regenerative medicine and mechanistic studies of chondrogenesis. Here, we demonstrate that chondrocytes are robustly induced from human PSCs by simple combination of two compounds, CHIR99021, a glycogen synthase kin...
Source: Stem Cell Reports - August 9, 2019 Category: Stem Cells Source Type: research

A Human Stem Cell Model of Fabry Disease Implicates LIMP-2 Accumulation in Cardiomyocyte Pathology
Publication date: Available online 1 August 2019Source: Stem Cell ReportsAuthor(s): Matthew J. Birket, Sophie Raibaud, Miriam Lettieri, Antony D. Adamson, Valerie Letang, Pauline Cervello, Nicolas Redon, Gwenaelle Ret, Sandra Viale, Bing Wang, Bruno Biton, Jean-Claude Guillemot, Vincent Mikol, John P. Leonard, Neil A. Hanley, Cecile Orsini, Jean-Michel ItierSummaryHere, we have used patient-derived induced pluripotent stem cell (iPSC) and gene-editing technology to study the cardiac-related molecular and functional consequences of mutations in GLA causing the lysosomal storage disorder Fabry disease (FD), for which he...
Source: Stem Cell Reports - August 2, 2019 Category: Stem Cells Source Type: research

Characterizing Direct-to-Consumer Stem Cell Businesses in the Southwest United States
Publication date: Available online 1 August 2019Source: Stem Cell ReportsAuthor(s): Emma K. Frow, David A. Brafman, Anna Muldoon, Logan Krum, Paige Williams, Bryson Becker, John P. Nelson, Ashley PritchettSummaryThere are currently hundreds of businesses across the United States offering direct-to-consumer stem cell treatments that have not been through regulatory approval by the Food and Drug Administration (FDA). Here, we provide a detailed characterization of nearly 170 stem cell businesses operating in the Southwest United States. We draw specific attention to two as-yet understudied facets of these businesses. First, ...
Source: Stem Cell Reports - August 2, 2019 Category: Stem Cells Source Type: research

Targeted Derivation of Organotypic Glucose- and GLP-1-Responsive β Cells Prior to Transplantation into Diabetic Recipients
Publication date: Available online 1 August 2019Source: Stem Cell ReportsAuthor(s): Yaxi Zhu, Jason M. Tonne, Qian Liu, Claire A. Schreiber, Zhiguang Zhou, Kuntol Rakshit, Aleksey V. Matveyenko, Andre Terzic, Dennis Wigle, Yogish C. Kudva, Yasuhiro IkedaSummaryGeneration of functional β cells from pluripotent sources would accelerate diagnostic and therapeutic applications for diabetes research and therapy. However, it has been challenging to generate competent β cells with dynamic insulin-secretory capacity to glucose and incretin stimulations. We introduced transcription factors, critical for β-cell develo...
Source: Stem Cell Reports - August 2, 2019 Category: Stem Cells Source Type: research

Gata2 as a Crucial Regulator of Stem Cells in Adult Hematopoiesis and Acute Myeloid Leukemia
Publication date: Available online 1 August 2019Source: Stem Cell ReportsAuthor(s): Juan Bautista Menendez-Gonzalez, Milica Vukovic, Ali Abdelfattah, Lubaid Saleh, Alhomidi Almotiri, Leigh-anne Thomas, Aloña Agirre-Lizaso, Aleksandra Azevedo, Ana Catarina Menezes, Giusy Tornillo, Sarah Edkins, Kay Kong, Peter Giles, Fernando Anjos-Afonso, Alex Tonks, Ashleigh S. Boyd, Kamil R. Kranc, Neil P. RodriguesSummarySubversion of transcription factor (TF) activity in hematopoietic stem/progenitor cells (HSPCs) leads to the development of therapy-resistant leukemic stem cells (LSCs) that drive fulminant acute myeloid leukemia...
Source: Stem Cell Reports - August 2, 2019 Category: Stem Cells Source Type: research

Phenotype-Based High-Throughput Classification of Long QT Syndrome Subtypes Using Human Induced Pluripotent Stem Cells
This study aimed to propose a phenotypic cell-based diagnostic assay for identifying LQTS to recognize pathogenic variants in a high-throughput manner suitable for screening. We investigated the response of LQT2-induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) following IKr blockade using a multi-electrode array, finding that the response to IKr blockade was significantly smaller than in Control-iPSC-CMs. Furthermore, we found that LQT1-iPSC-CMs and LQT3-iPSC-CMs could be distinguished from Control-iPSC-CMs by IKs blockade and INa blockade, respectively. This strategy might be helpful in compensating ...
Source: Stem Cell Reports - August 2, 2019 Category: Stem Cells Source Type: research

Long-Term Safety, Immunologic Response, and Imaging Outcomes following Neural Stem Cell Transplantation for Pelizaeus-Merzbacher Disease
Publication date: Available online 1 August 2019Source: Stem Cell ReportsAuthor(s): Nalin Gupta, Roland G. Henry, Sang-Mo Kang, Jonathan Strober, Daniel A. Lim, Tamara Ryan, Rachel Perry, Jody Farrell, Mary Ulman, Raja Rajalingam, Allyson Gage, Stephen L. Huhn, A. James Barkovich, David H. RowitchSummaryFour boys with Pelizaeus-Merzbacher disease, an X-linked leukodystrophy, underwent transplantation with human allogeneic central nervous system stem cells (HuCNS-SC). Subsequently, all subjects were followed for an additional 4 years in this separate follow-up study to evaluate safety, neurologic function, magnetic resonanc...
Source: Stem Cell Reports - August 2, 2019 Category: Stem Cells Source Type: research

Activin Is Superior to BMP7 for Efficient Maintenance of Human iPSC-Derived Nephron Progenitors
Publication date: Available online 1 August 2019Source: Stem Cell ReportsAuthor(s): Shunsuke Tanigawa, Hidekazu Naganuma, Yusuke Kaku, Takumi Era, Tetsushi Sakuma, Takashi Yamamoto, Atsuhiro Taguchi, Ryuichi NishinakamuraSummaryKidney formation is regulated by the balance between maintenance and differentiation of nephron progenitor cells (NPCs). Now that directed differentiation of NPCs from human induced pluripotent stem cells (iPSCs) can be achieved, maintenance and propagation of NPCs in vitro should be beneficial for regenerative medicine. Although WNT and FGF signals were previously shown to be essential for NPC...
Source: Stem Cell Reports - August 2, 2019 Category: Stem Cells Source Type: research

Downregulation of mTOR Signaling Increases Stem Cell Population Telomere Length during Starvation of Immortal Planarians
Publication date: Available online 25 July 2019Source: Stem Cell ReportsAuthor(s): Marta Iglesias, Daniel A. Felix, Óscar Gutiérrez-Gutiérrez, Maria del Mar De Miguel-Bonet, Sounak Sahu, Beatriz Fernández-Varas, Rosario Perona, A. Aziz Aboobaker, Ignacio Flores, Cristina González-EstévezSummaryReduction of caloric intake delays and prevents age-associated diseases and extends the life span in many organisms. It may be that these benefits are due to positive effects of caloric restriction on stem cell function. We use the planarian model Schmidtea mediterranea, an immortal animal th...
Source: Stem Cell Reports - July 26, 2019 Category: Stem Cells Source Type: research

Core Transcription Factors Promote Induction of PAX3-Positive Skeletal Muscle Stem Cells
Publication date: Available online 25 July 2019Source: Stem Cell ReportsAuthor(s): Takahiko Sato, Koki Higashioka, Hidetoshi Sakurai, Takuya Yamamoto, Naoki Goshima, Morio Ueno, Chie SotozonoSummaryThe use of adult skeletal muscle stem cells (MuSCs) for cell therapy has been attempted for decades, but still encounters considerable difficulties. MuSCs derived from human induced pluripotent stem cells (hiPSCs) are promising candidates for stem cell therapy to treat Duchenne muscular dystrophy (DMD). Here we report that four transcription factors, HEYL, KLF4, MYOD, and PAX3, selected by comprehensive screening of different Mu...
Source: Stem Cell Reports - July 26, 2019 Category: Stem Cells Source Type: research

Elevated Exogenous Pyruvate Potentiates Mesodermal Differentiation through Metabolic Modulation and AMPK/mTOR Pathway in Human Embryonic Stem Cells
This study reveals that exogenous pyruvate not only controls metabolism but also modulates signaling pathways in hESC differentiation.Graphical Abstract (Source: Stem Cell Reports)
Source: Stem Cell Reports - July 26, 2019 Category: Stem Cells Source Type: research

Continuous WNT Control Enables Advanced hPSC Cardiac Processing and Prognostic Surface Marker Identification in Chemically Defined Suspension Culture
Publication date: Available online 25 July 2019Source: Stem Cell ReportsAuthor(s): Caroline Halloin, Kristin Schw.e, Wiebke Löbel, Annika Franke, Monika Szepes, Santoshi Biswanath, Stephanie Wunderlich, Sylvia Merkert, Natalie Weber, Felix Osten, Jeanne de la Roche, Felix Polten, Kai Wollert, Theresia Kraft, Martin Fischer, Ulrich Martin, Ina Gruh, Henning Kempf, Robert ZweigerdtSummaryAiming at clinical translation, robust directed differentiation of human pluripotent stem cells (hPSCs), preferentially in chemically defined conditions, is a key requirement. Here, feasibility of suspension culture based hPSC-cardiomyo...
Source: Stem Cell Reports - July 26, 2019 Category: Stem Cells Source Type: research

CABLES1 Deficiency Impairs Quiescence and Stress Responses of Hematopoietic Stem Cells in Intrinsic and Extrinsic Manners
Publication date: Available online 18 July 2019Source: Stem Cell ReportsAuthor(s): Liang He, Florian Beghi, Viviane Baral, Mallorie Dépond, Yanyan Zhang, Virginie Joulin, Bo R. Rueda, Patrick Gonin, Adlen Foudi, Monika Wittner, Fawzia LouacheSummaryBone marrow (BM) niche cells help to keep adult hematopoietic stem cells (HSCs) in a quiescent state via secreted factors and induction of cell-cycle inhibitors. Here, we demonstrate that the adapter protein CABLES1 is a key regulator of long-term hematopoietic homeostasis during stress and aging. Young mice lacking Cables1 displayed hyperproliferation of hematopoietic pr...
Source: Stem Cell Reports - July 20, 2019 Category: Stem Cells Source Type: research

Cytokine Selection of MSC Clones with Different Functionality
Publication date: Available online 11 July 2019Source: Stem Cell ReportsAuthor(s): Anton Selich, Teng-Cheong Ha, Michael Morgan, Christine S. Falk, Constantin von Kaisenberg, Axel Schambach, Michael RotheSummaryMesenchymal stromal cells (MSCs) are used in many clinical applications. However, ex vivo expansion is required to reach clinically relevant cell numbers, which might lead to selection of clones with different characteristics. To follow clonal selection, we transduced MSC progenitors in umbilical cord pieces (UCPs) with vectors encoding fluorescent proteins and genetic barcodes. After marked MSC cultures grew o...
Source: Stem Cell Reports - July 12, 2019 Category: Stem Cells Source Type: research

In Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2 Using Human Induced Pluripotent Stem Cell-Derived Alveolar Organoids
Publication date: 9 July 2019Source: Stem Cell Reports, Volume 13, Issue 1Author(s): Yohei Korogi, Shimpei Gotoh, Satoshi Ikeo, Yuki Yamamoto, Naoyuki Sone, Koji Tamai, Satoshi Konishi, Tadao Nagasaki, Hisako Matsumoto, Isao Ito, Toyofumi F. Chen-Yoshikawa, Hiroshi Date, Masatoshi Hagiwara, Isao Asaka, Akitsu Hotta, Michiaki Mishima, Toyohiro Hirai (Source: Stem Cell Reports)
Source: Stem Cell Reports - July 11, 2019 Category: Stem Cells Source Type: research

Self-Organized Synchronous Calcium Transients in a Cultured Human Neural Network Derived from Cerebral Organoids
Publication date: Available online 27 June 2019Source: Stem Cell ReportsAuthor(s): Hideya Sakaguchi, Yuki Ozaki, Tomoka Ashida, Takayoshi Matsubara, Naotaka Oishi, Shunsuke Kihara, Jun TakahashiSummaryThe cerebrum is a major center for brain function, and its activity is derived from the assembly of activated cells in neural networks. It is currently difficult to study complex human cerebral neuronal network activity. Here, using cerebral organoids, we report self-organized and complex human neural network activities that include synchronized and non-synchronized patterns. Self-organized neuronal network formation was obse...
Source: Stem Cell Reports - June 29, 2019 Category: Stem Cells Source Type: research

Chemically Defined Media Can Maintain Pig Pluripotency Network In Vitro
Publication date: Available online 27 June 2019Source: Stem Cell ReportsAuthor(s): Kwang-Hwan Choi, Dong-Kyung Lee, Sung Woo Kim, Sang-Ho Woo, Dae-Yong Kim, Chang-Kyu LeeSummaryPig embryonic stem cells (pESCs) have been considered an important candidate for preclinical research on human therapies. However, the lack of understanding of pig pluripotent networks has hampered establishment of authentic pESCs. Here, we report that FGF2, ACTVIN, and WNT signaling are essential to sustain pig pluripotency in vitro. Newly derived pESCs were stably maintained over an extended period, and capable of forming teratomas that conta...
Source: Stem Cell Reports - June 29, 2019 Category: Stem Cells Source Type: research

Bmi1 Suppresses Adipogenesis in the Hematopoietic Stem Cell Niche
Publication date: Available online 27 June 2019Source: Stem Cell ReportsAuthor(s): Tianyuan Hu, Ayumi Kitano, Victor Luu, Brian Dawson, Kevin A. Hoegenauer, Brendan H. Lee, Daisuke NakadaSummaryBone marrow stromal cells (BMSCs) that express high levels of stem cell factor (SCF) and CXC chemokine ligand 12 (CXCL12) are one crucial component of the hematopoietic stem cell (HSC) niche. While the secreted factors produced by BMSCs to support HSCs have been well described, little is known regarding the transcriptional regulators controlling the cell fate of BMSCs and thus indirectly maintaining HSCs. BMI1 is a polycomb group pr...
Source: Stem Cell Reports - June 29, 2019 Category: Stem Cells Source Type: research

Breast Cancer Stem Cells with Tumor- versus Metastasis-Initiating Capacities Are Modulated by TGFBR1 Inhibition
Publication date: Available online 27 June 2019Source: Stem Cell ReportsAuthor(s): Flavia Fico, Mélanie Bousquenaud, Curzio Rüegg, Albert Santamaria-MartínezSummaryCancer stem cells (CSCs) are defined by their ability to regenerate a tumor upon transplantation. However, it is not yet clear whether tumors contain a single CSC population or different subsets of cells with mixed capacities for initiating primary and secondary tumors. Using two different identification strategies, we studied the overlap between metastatic stem cells and tumor-initiating cells (TICs) in the MMTV-PyMT model. Our results show t...
Source: Stem Cell Reports - June 29, 2019 Category: Stem Cells Source Type: research

Melanoma Progression Inhibits Pluripotency and Differentiation of Melanoma-Derived iPSCs Produces Cells with Neural-like Mixed Dysplastic Phenotype
Publication date: Available online 20 June 2019Source: Stem Cell ReportsAuthor(s): Edgardo Castro-Pérez, Carlos I. Rodríguez, Dareen Mikheil, Shakir Siddique, Alexandra McCarthy, Michael A. Newton, Vijayasaradhi SetaluriSummaryMelanomas are known to exhibit phenotypic plasticity. However, the role cellular plasticity plays in melanoma tumor progression and drug resistance is not fully understood. Here, we used reprogramming of melanocytes and melanoma cells to induced pluripotent stem cell (iPSCs) to investigate the relationship between cellular plasticity and melanoma progression and mitogen-activated protei...
Source: Stem Cell Reports - June 21, 2019 Category: Stem Cells Source Type: research

Hemogenic Endothelial Cells Can Transition to Hematopoietic Stem Cells through a B-1 Lymphocyte-Biased State during Maturation in the Mouse Embryo
Publication date: Available online 20 June 2019Source: Stem Cell ReportsAuthor(s): Michihiro Kobayashi, Stefan P. Tarnawsky, Haichao Wei, Akansha Mishra, Nathalia Azevedo Portilho, Pamela Wenzel, Brian Davis, Jiaqian Wu, Brandon Hadland, Momoko YoshimotoSummaryPrecursors of hematopoietic stem cells (pre-HSCs) have been identified as intermediate precursors during the maturation process from hemogenic endothelial cells to HSCs in the aorta-gonad-mesonephros (AGM) region of the mouse embryo at embryonic day 10.5. Although pre-HSCs acquire an efficient adult-repopulating ability after ex vivo co-culture, their native hem...
Source: Stem Cell Reports - June 21, 2019 Category: Stem Cells Source Type: research