Living with Keratinocytes
Publication date: 13 November 2018Source: Stem Cell Reports, Volume 11, Issue 5Author(s): Graziella Pellegrini, Michele De LucaA feature distinguishing human hematopoietic and epithelial stem cells from other equally fascinating stem cells is perhaps their easier translation into a clinical setting. We have devoted nearly our entire scientific career in trying to turn our understanding of epithelial stem cell biology into something that could help people suffering from virtually untreatable diseases of squamous epithelia. We have done that as a team, together with our numerous students, postdocs, technicians and valua...
Source: Stem Cell Reports - November 14, 2018 Category: Stem Cells Source Type: research

A Prospective Analysis of Human Leukemogenesis
Publication date: 13 November 2018Source: Stem Cell Reports, Volume 11, Issue 5Author(s): Connie J. EavesDecades of lack of progress in treating many fatal malignancies of the blood-forming system is commanding interest in new approaches. Targeting early events in the leukemogenic process has long been recognized as likely to offer the information required for these diseases. Analysis of the representation of different mutations in the leukemic cells from individual patients offers a retrospective method to infer their sequence of acquisition and associated subclonal dynamics. An alternative, prospective approach is to exp...
Source: Stem Cell Reports - November 14, 2018 Category: Stem Cells Source Type: research

Intestinal Stem Cells Exhibit Conditional Circadian Clock Function
Publication date: 13 November 2018Source: Stem Cell Reports, Volume 11, Issue 5Author(s): Kathyani Parasram, Nathaniel Bernardon, Maha Hammoud, Hanna Chang, Li He, Norbert Perrimon, Phillip KarpowiczSummaryThe circadian clock is a molecular pacemaker that produces 24-hr physiological cycles known as circadian rhythms. How the clock regulates stem cells is an emerging area of research with many outstanding questions. We tested clock function in vivo at the single cell resolution in the Drosophila intestine, a tissue that is exquisitely sensitive to environmental cues and has circadian rhythms in regeneration. Our resul...
Source: Stem Cell Reports - November 14, 2018 Category: Stem Cells Source Type: research

Tackling Ethical Challenges of Premature Delivery of Stem Cell-Based Therapies: ISSCR 2018 Annual Meeting Focus Session Report
Publication date: 13 November 2018Source: Stem Cell Reports, Volume 11, Issue 5Author(s): Jeremy Sugarman, Roger A. Barker, Ian Kerridge, Tamra Lysaght, Graziella Pellegrini, Douglas Sipp, Claire TannerClinical uses of unproven stem cell-based interventions abound, yet many patients may be harmed by receiving them, raising complex ethical, economic, and societal concerns. Regulators, scientists, clinicians, professional societies, and patient advocacy groups need to collaboratively articulate expectations related to the proper development and delivery of stem cell-based therapies. (Source: Stem Cell Reports)
Source: Stem Cell Reports - November 14, 2018 Category: Stem Cells Source Type: research

Excitable Adult-Generated GABAergic Neurons Acquire Functional Innervation in the Cortex after Stroke
Publication date: Available online 8 November 2018Source: Stem Cell ReportsAuthor(s): Timal S. Kannangara, Anthony Carter, Yingben Xue, Jagroop S. Dhaliwal, Jean-Claude Béïque, Diane C. LagaceSummaryIschemic stroke enhances the proliferation of adult-generated precursor cells that ectopically migrate toward the infarct. Studies have correlated precursor cell proliferation and subsequent adult neurogenesis with enhanced stroke recovery, yet it remains unclear whether stroke can generate new neurons capable of functional integration into the injured cortex. Here, using single and bitransgenic reporter mice, we id...
Source: Stem Cell Reports - November 9, 2018 Category: Stem Cells Source Type: research

Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium
Publication date: Available online 8 November 2018Source: Stem Cell ReportsAuthor(s): Marta Lemme, Bärbel M. Ulmer, Marc D. Lemoine, Antonia T.L. Zech, Frederik Flenner, Ursula Ravens, Hermann Reichenspurner, Miriam Rol-Garcia, Godfrey Smith, Arne Hansen, Torsten Christ, Thomas EschenhagenSummaryCardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs) are under investigation for their suitability as human models in preclinical drug development. Antiarrhythmic drug development focuses on atrial biology for the treatment of atrial fibrillation. Here we used recent retinoic acid-based protocols t...
Source: Stem Cell Reports - November 9, 2018 Category: Stem Cells Source Type: research

Patient-Specific iPSC-Derived Endothelial Cells Provide Long-Term Phenotypic Correction of Hemophilia A
Publication date: Available online 8 November 2018Source: Stem Cell ReportsAuthor(s): Cristina Olgasi, Maria Talmon, Simone Merlin, Alessia Cucci, Yvonne Richaud-Patin, Gabriella Ranaldo, Donato Colangelo, Federica Di Scipio, Giovanni N. Berta, Chiara Borsotti, Federica Valeri, Francesco Faraldi, Maria Prat, Maria Messina, Piercarla Schinco, Angelo Lombardo, Angel Raya, Antonia FollenziSummaryWe generated patient-specific disease-free induced pluripotent stem cells (iPSCs) from peripheral blood CD34+ cells and differentiated them into functional endothelial cells (ECs) secreting factor VIII (FVIII) for gene and cell therap...
Source: Stem Cell Reports - November 9, 2018 Category: Stem Cells Source Type: research

The Ubiquitin-Proteasome System Is Indispensable for the Maintenance of Muscle Stem Cells
Publication date: Available online 8 November 2018Source: Stem Cell ReportsAuthor(s): Yasuo Kitajima, Naoki Suzuki, Aki Nunomiya, Shion Osana, Kiyoshi Yoshioka, Yoshitaka Tashiro, Ryosuke Takahashi, Yusuke Ono, Masashi Aoki, Ryoichi NagatomiSummaryAdult muscle stem cells (satellite cells) are required for adult skeletal muscle regeneration. A proper balance between quiescence, proliferation, and differentiation is essential for the maintenance of the satellite cell pool and their regenerative function. Although the ubiquitin-proteasome is required for most protein degradation in mammalian cells, how its dysfunction affects...
Source: Stem Cell Reports - November 9, 2018 Category: Stem Cells Source Type: research

Isogenic Pairs of hiPSC-CMs with Hypertrophic Cardiomyopathy/LVNC-Associated ACTC1 E99K Mutation Unveil Differential Functional Deficits
Publication date: Available online 1 November 2018Source: Stem Cell ReportsAuthor(s): James G.W. Smith, Thomas Owen, Jamie R. Bhagwan, Diogo Mosqueira, Elizabeth Scott, Ingra Mannhardt, Asha Patel, Roberto Barriales-Villa, Lorenzo Monserrat, Arne Hansen, Thomas Eschenhagen, Sian E. Harding, Steve Marston, Chris DenningSummaryHypertrophic cardiomyopathy (HCM) is a primary disorder of contractility in heart muscle. To gain mechanistic insight and guide pharmacological rescue, this study models HCM using isogenic pairs of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying the E99K-ACTC1 cardiac ac...
Source: Stem Cell Reports - November 2, 2018 Category: Stem Cells Source Type: research

Complete Disruption of Autism-Susceptibility Genes by Gene Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons
We present a CRISPR gene editing strategy to insert a protein tag and premature termination sites creating an induced pluripotent stem cell (iPSC) knockout resource for functional studies of ten ASD-relevant genes (AFF2/FMR2, ANOS1, ASTN2, ATRX, CACNA1C, CHD8, DLGAP2, KCNQ2, SCN2A, TENM1). Neurogenin 2 (NGN2)-directed induction of iPSCs allowed production of excitatory neurons, and mutant proteins were not detectable. RNA sequencing revealed convergence of several neuronal networks. Using both patch-clamp and multi-electrode array approaches, the electrophysiological deficits measured were distinct for different mutations....
Source: Stem Cell Reports - November 2, 2018 Category: Stem Cells Source Type: research

An mTOR Signaling Modulator Suppressed Heterotopic Ossification of Fibrodysplasia Ossificans Progressiva
Publication date: Available online 1 November 2018Source: Stem Cell ReportsAuthor(s): Kyosuke Hino, Chengzhu Zhao, Kazuhiko Horigome, Megumi Nishio, Yasue Okanishi, Sanae Nagata, Shingo Komura, Yasuhiro Yamada, Junya Toguchida, Akira Ohta, Makoto IkeyaSummaryFibrodysplasia ossificans progressiva (FOP) is a rare and intractable disorder characterized by extraskeletal bone formation through endochondral ossification. FOP patients harbor gain-of-function mutations in ACVR1 (FOP-ACVR1), a type I receptor for bone morphogenetic proteins. Despite numerous studies, no drugs have been approved for FOP. Here, we developed a high-th...
Source: Stem Cell Reports - November 2, 2018 Category: Stem Cells Source Type: research

Generation of Progesterone-Responsive Endometrial Stromal Fibroblasts from Human Induced Pluripotent Stem Cells: Role of the WNT/CTNNB1 Pathway
Publication date: Available online 1 November 2018Source: Stem Cell ReportsAuthor(s): Kaoru Miyazaki, Matthew T. Dyson, John S. Coon V, Yuichi Furukawa, Bahar D. Yilmaz, Tetsuo Maruyama, Serdar E. BulunSummaryDefective endometrial stromal fibroblasts (EMSFs) contribute to uterine factor infertility, endometriosis, and endometrial cancer. Induced pluripotent stem cells (iPSCs) derived from skin or bone marrow biopsies provide a patient-specific source that can be differentiated to various cells types. Replacement of abnormal EMSFs is a potential novel therapeutic approach for endometrial disease; however, the methodology or...
Source: Stem Cell Reports - November 2, 2018 Category: Stem Cells Source Type: research

Proteinase 3 Limits the Number of Hematopoietic Stem and Progenitor Cells in Murine Bone Marrow
Publication date: Available online 1 November 2018Source: Stem Cell ReportsAuthor(s): Kutay Karatepe, Haiyan Zhu, Xiaoyu Zhang, Rongxia Guo, Hiroto Kambara, Fabien Loison, Peng Liu, Hongbo Yu, Qian Ren, Xiao Luo, John Manis, Tao Cheng, Fengxia Ma, Yuanfu Xu, Hongbo R. LuoSummaryHematopoietic stem and progenitor cells (HSPCs) undergo self-renewal and differentiation to guarantee a constant supply of short-lived blood cells. Both intrinsic and extrinsic factors determine HSPC fate, but the underlying mechanisms remain elusive. Here, we report that Proteinase 3 (PR3), a serine protease mainly confined to granulocytes, is...
Source: Stem Cell Reports - November 2, 2018 Category: Stem Cells Source Type: research

Genetic Engineering of Human Embryonic Stem Cells for Precise Cell Fate Tracing during Human Lineage Development
Publication date: Available online 25 October 2018Source: Stem Cell ReportsAuthor(s): Zhenyu Chen, Xudong Ren, Xiangjie Xu, Xiaojie Zhang, Yi Hui, Zhongliang Liu, Lei Shi, Yujiang Fang, Lin Ma, Yang Liu, Daniel Terheyden-Keighley, Ling Liu, Xiaoqing ZhangSummaryIt is highly desirable to specify human developmental principles in an appropriate human model with advanced genetic tools. However, genetically engineering human cells with lineage-tracing systems has not been achieved. Here we introduce strategies to construct lineage-tracing systems in human embryonic stem cells (hESCs). The AAVS1 locus was suitable for the integ...
Source: Stem Cell Reports - October 26, 2018 Category: Stem Cells Source Type: research

Human Induced Pluripotent Stem Cell-Derived Astrocytes Are Differentially Activated by Multiple Sclerosis-Associated Cytokines
Publication date: Available online 25 October 2018Source: Stem Cell ReportsAuthor(s): Sylvain Perriot, Amandine Mathias, Guillaume Perriard, Mathieu Canales, Nils Jonkmans, Nicolas Merienne, Cécile Meunier, Lina El Kassar, Anselme L. Perrier, David-Axel Laplaud, Myriam Schluep, Nicole Déglon, Renaud Du PasquierSummaryRecent studies highlighted the importance of astrocytes in neuroinflammatory diseases, interacting closely with other CNS cells but also with the immune system. However, due to the difficulty in obtaining human astrocytes, their role in these pathologies is still poorly characterized. Here, we de...
Source: Stem Cell Reports - October 26, 2018 Category: Stem Cells Source Type: research

Early Human Hemogenic Endothelium Generates Primitive and Definitive Hematopoiesis In Vitro
Publication date: Available online 25 October 2018Source: Stem Cell ReportsAuthor(s): Eva Garcia-Alegria, Sara Menegatti, Muhammad Z.H. Fadlullah, Pablo Menendez, Georges Lacaud, Valerie KouskoffSummaryThe differentiation of human embryonic stem cells (hESCs) to hematopoietic lineages initiates with the specification of hemogenic endothelium, a transient specialized endothelial precursor of all blood cells. This in vitro system provides an invaluable model to dissect the emergence of hematopoiesis in humans. However, the study of hematopoiesis specification is hampered by a lack of consensus in the timing of hemo...
Source: Stem Cell Reports - October 26, 2018 Category: Stem Cells Source Type: research

Studies in an Early Development Window Unveils a Severe HSC Defect in both Murine and Human Fanconi Anemia
This study reveals a deep HSC defect with exhaustion of proliferative and self-renewal capacities very early during development, together with severe FA clinical and biological manifestations, which are mitigated at E14.5 due to compensatory mechanisms that help to ensure survival of Fancg−/− embryos. It also reports that a deep HSC defect is also observed during human FA development, and that human FA fetal liver (FL) HSCs present a transcriptome profile similar to that of mouse E12.5 Fancg−/− FL HSCs. Altogether, our results highlight that early mouse FL could represent a good alternative model fo...
Source: Stem Cell Reports - October 26, 2018 Category: Stem Cells Source Type: research

The SCRIB Paralog LANO/LRRC1 Regulates Breast Cancer Stem Cell Fate through WNT/β-Catenin Signaling
Publication date: Available online 18 October 2018Source: Stem Cell ReportsAuthor(s): Leonor Lopez Almeida, Michael Sebbagh, François Bertucci, Pascal Finetti, Julien Wicinski, Sylvie Marchetto, Rémy Castellano, Emmanuelle Josselin, Emmanuelle Charafe-Jauffret, Christophe Ginestier, Jean-Paul Borg, Marie-Josée SantoniSummaryTumor initiation, progression, and therapeutic resistance have been proposed to originate from a subset of tumor cells, cancer stem cells (CSCs). However, the current understanding of the mechanisms involved in their self-renewal and tumor initiation capacity remains limited. Here, ...
Source: Stem Cell Reports - October 19, 2018 Category: Stem Cells Source Type: research

Mitochondrial Dysregulation and Impaired Autophagy in iPSC-Derived Dopaminergic Neurons of Multiple System Atrophy
Publication date: Available online 18 October 2018Source: Stem Cell ReportsAuthor(s): Giacomo Monzio Compagnoni, Giulio Kleiner, Maura Samarani, Massimo Aureli, Gaia Faustini, Arianna Bellucci, Dario Ronchi, Andreina Bordoni, Manuela Garbellini, Sabrina Salani, Francesco Fortunato, Emanuele Frattini, Elena Abati, Christian Bergamini, Romana Fato, Silvia Tabano, Monica Miozzo, Giulia Serratto, Maria Passafaro, Michela DeleidiSummaryMultiple system atrophy (MSA) is a progressive neurodegenerative disease that affects several areas of the CNS, whose pathogenesis is still widely unclear and for which an effective treatment is ...
Source: Stem Cell Reports - October 19, 2018 Category: Stem Cells Source Type: research

Connexin 43-Mediated Mitochondrial Transfer of iPSC-MSCs Alleviates Asthma Inflammation
This study provides a therapeutic strategy for targeting asthma inflammation.Graphical Abstract (Source: Stem Cell Reports)
Source: Stem Cell Reports - October 19, 2018 Category: Stem Cells Source Type: research

T-type Calcium Channels Determine the Vulnerability of Dopaminergic Neurons to Mitochondrial Stress in Familial Parkinson Disease
In this study, we generated DA neurons from PARK2 patient-specific, isogenic PARK2 null and PARK6 patient-specific induced pluripotent stem cells and found that these neurons exhibited more apoptosis and greater susceptibility to rotenone-induced mitochondrial stress. From phenotypic screening with an FDA-approved drug library, one voltage-gated calcium channel antagonist, benidipine, was found to suppress rotenone-induced apoptosis. Furthermore, we demonstrated the dysregulation of calcium homeostasis and increased susceptibility to rotenone-induced stress in PD, which is prevented by T-type calcium channel knockdown or a...
Source: Stem Cell Reports - October 19, 2018 Category: Stem Cells Source Type: research

Human Teratoma-Derived Hematopoiesis Is a Highly Polyclonal Process Supported by Human Umbilical Vein Endothelial Cells
In this study, a feasible protocol for robust hematopoiesis has been elaborated. We achieved a significant increase of the teratoma-derived hematopoietic population when teratomas were generated in the NSGS mouse, which provides human cytokines, together with co-injection of human umbilical vein endothelial cells. Since little is known about hematopoiesis in teratomas, we addressed localization and clonality of the hematopoietic lineage. Our results indicate that early human hematopoiesis is closely reflected in teratoma formation, and thus highlight the value of this model.Graphical Abstract (Source: Stem Cell Reports)
Source: Stem Cell Reports - October 19, 2018 Category: Stem Cells Source Type: research

NANOG Is Required for the Long-Term Establishment of Avian Somatic Reprogrammed Cells
In conclusion, although the somatic reprogramming process is active in avian primary cells, it needs to be optimized to obtain fully reprogrammed cells with similar properties to those of chicken embryonic stem cells. (Source: Stem Cell Reports)
Source: Stem Cell Reports - October 12, 2018 Category: Stem Cells Source Type: research

Phenotypic Reprogramming of Striatal Neurons into Dopaminergic Neuron-like Cells in the Adult Mouse Brain
Publication date: Available online 11 October 2018Source: Stem Cell ReportsAuthor(s): Wenze Niu, Tong Zang, Lei-Lei Wang, Yuhua Zou, Chun-Li ZhangSummaryNeuronal subtype is largely fixed in the adult mammalian brain. Here, however, we unexpectedly reveal that adult mouse striatal neurons can be reprogrammed into dopaminergic neuron-like cells (iDALs). This in vivo phenotypic reprogramming can be promoted by a stem cell factor (SOX2), three dopaminergic neuron-enriched transcription regulators (NURR1, LMX1A, and FOXA2), and a chemical compound (valproic acid). Although the site of action of the reprogramming factors re...
Source: Stem Cell Reports - October 12, 2018 Category: Stem Cells Source Type: research

Women in Stem Cell Science: Part II
Publication date: 9 October 2018Source: Stem Cell Reports, Volume 11, Issue 4Author(s): Part II of this series continues a focus on top female researchers in the stem cell field, with personal stories and reflections on career paths. Women play key roles as leaders in the field and with the International Society for Stem Cell Research. Part I was published in the September 2018 issue of Stem Cell Reports. (Source: Stem Cell Reports)
Source: Stem Cell Reports - October 10, 2018 Category: Stem Cells Source Type: research

Quick Access to Human Astrocytic Software that Drives Neuronal Hardware
Publication date: 9 October 2018Source: Stem Cell Reports, Volume 11, Issue 4Author(s): Anders Lundin, Anna FalkAstrocytes have important functions in the brain and their deregulation may cause disease. Current ways to derive astrocytes from pluripotent stem cells are labor, time, and resource intensive, but in this issue of Stem Cell Reports, Li et al. present a faster method to produce functional astrocytes using transcription factors. (Source: Stem Cell Reports)
Source: Stem Cell Reports - October 10, 2018 Category: Stem Cells Source Type: research

Regenerative Medicine: Taming the Chimaera
Publication date: 9 October 2018Source: Stem Cell Reports, Volume 11, Issue 4Author(s): Bernard A.J. RoelenIn this issue of Stem Cell Reports, Hamanaka et al. (2018) describe the generation of chimeric mice with all vascular endothelial cells derived from pluripotent stem cells. This approach is desirable to prevent immune rejection when human stem cells are combined with animal embryos to grow human organs in animals. (Source: Stem Cell Reports)
Source: Stem Cell Reports - October 10, 2018 Category: Stem Cells Source Type: research

Selective Elimination of Culture-Adapted Human Embryonic Stem Cells with BH3 Mimetics
Publication date: Available online 4 October 2018Source: Stem Cell ReportsAuthor(s): Seung-Ju Cho, Keun-Tae Kim, Ho-Chang Jeong, Ju-Chan Park, Ok-Seon Kwon, Yun-Ho Song, Joong-Gon Shin, Seungmin Kang, W.yu Kim, Hyoung Doo Shin, Mi-Ok Lee, Sung-Hwan Moon, Hyuk-Jin ChaSummaryThe selective survival advantage of culture-adapted human embryonic stem cells (hESCs) is a serious safety concern for their clinical application. With a set of hESCs with various passage numbers, we observed that a subpopulation of hESCs at late passage numbers was highly resistant to various cell death stimuli, such as YM155, a survivin inhibitor. Tran...
Source: Stem Cell Reports - October 5, 2018 Category: Stem Cells Source Type: research

Disruption of OCT4 Ubiquitination Increases OCT4 Protein Stability and ASH2L-B-Mediated H3K4 Methylation Promoting Pluripotency Acquisition
Publication date: Available online 27 September 2018Source: Stem Cell ReportsAuthor(s): Shuang Li, Feng Xiao, Junmei Zhang, Xiaozhi Sun, Han Wang, Yanwu Zeng, Jing Hu, Fan Tang, Junjie Gu, Yingming Zhao, Ying Jin, Bing LiaoSummaryThe protein level of OCT4, a core pluripotency transcription factor, is vital for embryonic stem cell (ESC) maintenance, differentiation, and somatic cell reprogramming. However, how OCT4 protein levels are controlled during reprogramming remains largely unknown. Here, we identify ubiquitin conjugation sites of OCT4 and report that disruption of WWP2-catalyzed OCT4 ubiquitination or ablation of Ww...
Source: Stem Cell Reports - October 4, 2018 Category: Stem Cells Source Type: research

Fast Generation of Functional Subtype Astrocytes from Human Pluripotent Stem Cells
Publication date: Available online 27 September 2018Source: Stem Cell ReportsAuthor(s): Xiang Li, Yezheng Tao, Robert Bradley, Zhongwei Du, Yunlong Tao, Linghai Kong, Yi Dong, Jeffrey Jones, Yuanwei Yan, Cole R.K. Harder, Lindsay Morgan Friedman, Magd Bilal, Brianna Hoffmann, Su-Chun ZhangSummaryDifferentiation of astrocytes from human pluripotent stem cells (hPSCs) is a tedious and variable process. This hampers the study of hPSC-generated astrocytes in disease processes and drug development. By using CRISPR/Cas9-mediated inducible expression of NFIA or NFIA plus SOX9 in hPSCs, we developed a method to efficiently generat...
Source: Stem Cell Reports - October 4, 2018 Category: Stem Cells Source Type: research

Reproducibility of Molecular Phenotypes after Long-Term Differentiation to Human iPSC-Derived Neurons: A Multi-Site Omics Study
Publication date: Available online 20 September 2018Source: Stem Cell ReportsAuthor(s): Viola Volpato, James Smith, Cynthia Sandor, Janina S. Ried, Anna Baud, Adam Handel, Sarah E. Newey, Frank Wessely, Moustafa Attar, Emma Whiteley, Satyan Chintawar, An Verheyen, Thomas Barta, Majlinda Lako, Lyle Armstrong, Caroline Muschet, Anna Artati, Carlo Cusulin, Klaus Christensen, Christoph PatschSummaryReproducibility in molecular and cellular studies is fundamental to scientific discovery. To establish the reproducibility of a well-defined long-term neuronal differentiation protocol, we repeated the cellular and molecular compari...
Source: Stem Cell Reports - September 21, 2018 Category: Stem Cells Source Type: research

Hsp83/Hsp90 Physically Associates with Insulin Receptor to Promote Neural Stem Cell Reactivation
Publication date: Available online 20 September 2018Source: Stem Cell ReportsAuthor(s): Jiawen Huang, Hongyan WangSummaryNeural stem cells (NSCs) have the ability to exit quiescence and reactivate in response to physiological stimuli. In the Drosophila brain, insulin receptor (InR)/phosphatidylinositol 3-kinase (PI3K)/Akt pathway triggers NSC reactivation. However, intrinsic mechanisms that control the InR/PI3K/Akt pathway during reactivation remain unknown. Here, we have identified heat shock protein 83 (Hsp83/Hsp90), a molecular chaperone, as an intrinsic regulator of NSC reactivation. Hsp83 is both necessary and suffici...
Source: Stem Cell Reports - September 21, 2018 Category: Stem Cells Source Type: research

Generation of Vascular Endothelial Cells and Hematopoietic Cells by Blastocyst Complementation
Publication date: Available online 20 September 2018Source: Stem Cell ReportsAuthor(s): Sanae Hamanaka, Ayumi Umino, Hideyuki Sato, Tomonari Hayama, Ayaka Yanagida, Naoaki Mizuno, Toshihiro Kobayashi, Mariko Kasai, Fabian Patrik Suchy, Satoshi Yamazaki, Hideki Masaki, Tomoyuki Yamaguchi, Hiromitsu NakauchiSummaryIn the case of organ transplantation accompanied by vascular anastomosis, major histocompatibility complex mismatched vascular endothelial cells become a target for graft rejection. Production of a rejection-free, transplantable organ, therefore, requires simultaneous generation of vascular endothelial cells within...
Source: Stem Cell Reports - September 21, 2018 Category: Stem Cells Source Type: research

Crosstalk between BPA and FXRα Signaling Pathways Lead to Alterations of Undifferentiated Germ Cell Homeostasis and Male Fertility Disorders
Publication date: Available online 20 September 2018Source: Stem Cell ReportsAuthor(s): Lauriane Sèdes, Christèle Desdoits-Lethimonier, Betty Rouaisnel, Hélène Holota, Laura Thirouard, Laurianne Lesne, Christelle Damon-Soubeyrand, Emmanuelle Martinot, Jean-Paul Saru, Séverine Mazaud-Guittot, Françoise Caira, Claude Beaudoin, Bernard Jégou, David H. VolleSummarySeveral studies have reported an association between the farnesoid X receptor alpha (FXRα) and estrogenic signaling pathways. Fxrα could thus be involved in the reprotoxic effects of endocrine dis...
Source: Stem Cell Reports - September 21, 2018 Category: Stem Cells Source Type: research

Targeting the Extracellular Signal-Regulated Kinase 5 Pathway to Suppress Human Chronic Myeloid Leukemia Stem Cells
Publication date: Available online 20 September 2018Source: Stem Cell ReportsAuthor(s): Ignazia Tusa, Giulia Cheloni, Martina Poteti, Antonella Gozzini, Ngoc Ho DeSouza, Yi Shan, Xianming Deng, Nathanael S. Gray, Shaoguang Li, Elisabetta Rovida, Persio Dello SbarbaSummaryTyrosine kinase inhibitors (TKi) are effective against chronic myeloid leukemia (CML), but their inefficacy on leukemia stem cells (LSCs) may lead to relapse. To identify new druggable targets alternative to BCR/ABL, we investigated the role of the MEK5/ERK5 pathway in LSC maintenance in low oxygen, a feature of bone marrow stem cell niches. We found that ...
Source: Stem Cell Reports - September 21, 2018 Category: Stem Cells Source Type: research

Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation
Publication date: Available online 13 September 2018Source: Stem Cell ReportsAuthor(s): Anneliis Ihermann-Hella, Tsuyoshi Hirashima, Jussi Kupari, Kristen Kurtzeborn, Hao Li, Hyuk Nam Kwon, Cristina Cebrian, Abdul Soofi, Arvydas Dapkunas, Ilkka Miinalainen, Gregory R. Dressler, Michiyuki Matsuda, Satu KuureSummaryThe in vivo niche and basic cellular properties of nephron progenitors are poorly described. Here we studied the cellular organization and function of the MAPK/ERK pathway in nephron progenitors. Live-imaging of ERK activity by a Förster resonance energy transfer biosensor revealed a dynamic activation p...
Source: Stem Cell Reports - September 14, 2018 Category: Stem Cells Source Type: research

Women in Stem Cell Science: Part I
Publication date: 11 September 2018Source: Stem Cell Reports, Volume 11, Issue 3Author(s): Female scientists play important leadership roles in the field and with the International Society for Stem Cell Research. We asked a number of these top researchers to share their personal stories and reflect on their career paths. Part II of this series will run in the October 2018 issue of Stem Cell Reports. (Source: Stem Cell Reports)
Source: Stem Cell Reports - September 12, 2018 Category: Stem Cells Source Type: research

iPSC-Based Disease Modeling and Drug Screening: An Interview with Paul Tesar and Matthew Elitt
Publication date: 11 September 2018Source: Stem Cell Reports, Volume 11, Issue 3Author(s): This month we present a new Q&A with Paul Tesar, DPhil, Associate Professor and Director of the Pluripotent Stem Cell Facility at Case Western Reserve University (U.S.). Dr. Tesar is a recipient of the Beddington Medal of the British Society for Developmental Biology and the 2015 recipient of the ISSCR’s Young Investigator Award. Stem Cell Reports has invited Dr. Tesar and graduate student Matthew Elitt, the first author of Elitt et al. (in this issue of Stem Cell Reports), to answer some questions about their publicat...
Source: Stem Cell Reports - September 12, 2018 Category: Stem Cells Source Type: research

Analysis of Runx1 Using Induced Gene Ablation Reveals Its Essential Role in Pre-liver HSC Development and Limitations of an In Vivo Approach
Publication date: 11 September 2018Source: Stem Cell Reports, Volume 11, Issue 3Author(s): Jordi Senserrich, Antoniana Batsivari, Stanislav Rybtsov, Sabrina Gordon-Keylock, Celine Souilhol, Frank Buchholz, David Hills, Suling Zhao, Alexander MedvinskySummaryHematopoietic stem cells (HSCs) develop in the embryonic aorta-gonad-mesonephros (AGM) region and subsequently relocate to fetal liver. Runx1 transcription factor is essential for HSC development, but is largely dispensable for adult HSCs. Here, we studied tamoxifen-inducible Runx1 inactivation in vivo. Induction at pre-liver stages (up to embryonic day 10.5) reduc...
Source: Stem Cell Reports - September 12, 2018 Category: Stem Cells Source Type: research

Cell Surface N-Glycans Influence Electrophysiological Properties and Fate Potential of Neural Stem Cells
Publication date: Available online 6 September 2018Source: Stem Cell ReportsAuthor(s): Andrew R. Yale, Jamison L. Nourse, Kayla R. Lee, Syed N. Ahmed, Janahan Arulmoli, Alan Y.L. Jiang, Lisa P. McDonnell, Giovanni A. Botten, Abraham P. Lee, Edwin S. Monuki, Michael Demetriou, Lisa A. FlanaganSummaryUnderstanding the cellular properties controlling neural stem and progenitor cell (NSPC) fate choice will improve their therapeutic potential. The electrophysiological measure whole-cell membrane capacitance reflects fate bias in the neural lineage but the cellular properties underlying membrane capacitance are poorly understood...
Source: Stem Cell Reports - September 7, 2018 Category: Stem Cells Source Type: research

Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells
Publication date: Available online 6 September 2018Source: Stem Cell ReportsAuthor(s): Tereza Renzova, Dasa Bohaciakova, Milan Esner, Veronika Pospisilova, Tomas Barta, Ales Hampl, Lukas CajanekSummaryCentrioles account for centrosomes and cilia formation. Recently, a link between centrosomal components and human developmental disorders has been established. However, the exact mechanisms how centrosome abnormalities influence embryogenesis and cell fate are not understood. PLK4-STIL module represents a key element of centrosome duplication cycle. We analyzed consequences of inactivation of the module for early events of em...
Source: Stem Cell Reports - September 7, 2018 Category: Stem Cells Source Type: research

Activation of Intrinsic Growth State Enhances Host Axonal Regeneration into Neural Progenitor Cell Grafts
We examined whether activation of the growth state of the host injured neuron would elicit greater regeneration into NPC grafts. Rats received NPC grafts into SCI lesions in combination with peripheral “conditioning” lesions. Six weeks later, conditioned host sensory axons exhibited a significant, 9.6-fold increase in regeneration into the lesion/graft site compared with unconditioned axons. Regeneration was further enhanced 1.6-fold by enriching NPC grafts with phenotypically appropriate sensory neuronal targets. Thus, activation of the intrinsic host neuronal growth state and manipulation of the graft environ...
Source: Stem Cell Reports - September 7, 2018 Category: Stem Cells Source Type: research

Rapid Mast Cell Generation from Gata2 Reporter Pluripotent Stem Cells
Publication date: Available online 6 September 2018Source: Stem Cell ReportsAuthor(s): Mari-Liis Kauts, Bianca De Leo, Carmen Rodríguez-Seoane, Roger Ronn, Fokion Glykofrydis, Antonio Maglitto, Polynikis Kaimakis, Margarita Basi, Helen Taylor, Lesley Forrester, Adam C. Wilkinson, Berthold Göttgens, Philippa Saunders, Elaine DzierzakSummaryMast cells are tissue-resident immune cells. Their overgrowth/overactivation results in a range of common distressing, sometimes life-threatening disorders, including asthma, psoriasis, anaphylaxis, and mastocytosis. Currently, drug discovery is hampered by use of cancer-deriv...
Source: Stem Cell Reports - September 7, 2018 Category: Stem Cells Source Type: research

Defining Lineage-Specific Membrane Fluidity Signatures that Regulate Adhesion Kinetics
Publication date: Available online 6 September 2018Source: Stem Cell ReportsAuthor(s): Takahisa Matsuzaki, Shinya Matsumoto, Toshiharu Kasai, Emi Yoshizawa, Satoshi Okamoto, Hiroshi Y. Yoshikawa, Hideki Taniguchi, Takanori TakebeSummaryCellular membrane fluidity is a critical modulator of cell adhesion and migration, prompting us to define the systematic landscape of lineage-specific cellular fluidity throughout differentiation. Here, we have unveiled membrane fluidity landscapes in various lineages ranging from human pluripotency to differentiated progeny: (1) membrane rigidification precedes the exit from pluripotency, (...
Source: Stem Cell Reports - September 7, 2018 Category: Stem Cells Source Type: research

HOPX Defines Heterogeneity of Postnatal Subventricular Zone Neural Stem Cells
Publication date: Available online 30 August 2018Source: Stem Cell ReportsAuthor(s): Stefan Zweifel, Guillaume Marcy, Quentin Lo Guidice, Deqiang Li, Christophe Heinrich, Kasum Azim, Olivier RaineteauSummaryThe largest diversity of neural lineages generated from the subventricular zone (SVZ) occurs early after birth and is regulated in a spatiotemporal manner depending on the expression of specific transcriptional cues. Transcriptomics and fate-mapping approaches were employed to explore the relationship between regional expression of transcription factors by neural stem cells (NSCs) and the specification of distinct neura...
Source: Stem Cell Reports - September 1, 2018 Category: Stem Cells Source Type: research

A Chemical Recipe for Generation of Clinical-Grade Striatal Neurons from hESCs
Publication date: Available online 30 August 2018Source: Stem Cell ReportsAuthor(s): Menghua Wu, Da Zhang, Chunying Bi, Tingwei Mi, Wenliang Zhu, Longkuo Xia, Zhaoqian Teng, Baoyang Hu, Yihui WuSummaryDifferentiation of human pluripotent stem cells (hPSCs) into striatal medium spiny neurons (MSNs) promises a cell-based therapy for Huntington's disease. However, clinical-grade MSNs remain unavailable. Here, we developed a chemical recipe named XLSBA to generate clinical-grade MSNs from embryonic stem cells (ESCs). We introduced the γ-secretase inhibitor DAPT into the recipe to accelerate neural differentiati...
Source: Stem Cell Reports - September 1, 2018 Category: Stem Cells Source Type: research

The microRNA miR-21 Is a Mediator of FGF8 Action on Cortical COUP-TFI Translation
Publication date: Available online 30 August 2018Source: Stem Cell ReportsAuthor(s): Marco Terrigno, Michele Bertacchi, Luca Pandolfini, Mario Baumgart, Mariantonietta Calvello, Alessandro Cellerino, Michèle Studer, Federico CremisiSummaryThe morphogen FGF8 plays a pivotal role in neocortical area patterning through its inhibitory effect on COUP-TFI/Nr2f1 anterior expression, but its mechanism of action is poorly understood. We established an in vitro model of mouse embryonic stem cell corticogenesis in which COUP-TFI protein expression is inhibited by the activation of FGF8 in a time window corresponding to co...
Source: Stem Cell Reports - September 1, 2018 Category: Stem Cells Source Type: research

Organoids from Nephrotic Disease-Derived iPSCs Identify Impaired NEPHRIN Localization and Slit Diaphragm Formation in Kidney Podocytes
Publication date: Available online 30 August 2018Source: Stem Cell ReportsAuthor(s): Shunsuke Tanigawa, Mazharul Islam, Sazia Sharmin, Hidekazu Naganuma, Yasuhiro Yoshimura, Fahim Haque, Takumi Era, Hitoshi Nakazato, Koichi Nakanishi, Tetsushi Sakuma, Takashi Yamamoto, Hidetake Kurihara, Atsuhiro Taguchi, Ryuichi NishinakamuraSummaryMutations in the NPHS1 gene, which encodes NEPHRIN, cause congenital nephrotic syndrome, resulting from impaired slit diaphragm (SD) formation in glomerular podocytes. However, methods for SD reconstitution have been unavailable, thereby limiting studies in the field. In the present study, we e...
Source: Stem Cell Reports - September 1, 2018 Category: Stem Cells Source Type: research

The Long Noncoding RNA Lncenc1 Maintains Naive States of Mouse ESCs by Promoting the Glycolysis Pathway
Publication date: Available online 30 August 2018Source: Stem Cell ReportsAuthor(s): Zihao Sun, Minzhe Zhu, Pin Lv, Lu Cheng, Qianfeng Wang, Pengxiang Tian, Zixiang Yan, Bo WenSummaryThe naive embryonic stem cells (nESCs) display unique characteristics compared with the primed counterparts, but the underlying molecular mechanisms remain elusive. Here we investigate the functional roles of Lncenc1, a highly abundant long noncoding RNA in nESCs. Knockdown or knockout of Lncenc1 in mouse nESCs leads to a significantly decreased expression of core pluripotency genes and a significant reduction of colony formation capability. F...
Source: Stem Cell Reports - September 1, 2018 Category: Stem Cells Source Type: research

Channelopathy as a SUDEP Biomarker in Dravet Syndrome Patient-Derived Cardiac Myocytes
Publication date: Available online 23 August 2018Source: Stem Cell ReportsAuthor(s): Chad R. Frasier, Helen Zhang, James Offord, Louis T. Dang, David S. Auerbach, Huilin Shi, Chunling Chen, Alica M. Goldman, L. Lee Eckhardt, Vassilios J. Bezzerides, Jack M. Parent, Lori L. IsomSummaryDravet syndrome (DS) is a severe developmental and epileptic encephalopathy with a high incidence of sudden unexpected death in epilepsy (SUDEP). Most DS patients carry de novo variants in SCN1A, resulting in Nav1.1 haploinsufficiency. Because SCN1A is expressed in heart and in brain, we proposed that cardiac arrhythmia contributes to SUDEP in...
Source: Stem Cell Reports - August 24, 2018 Category: Stem Cells Source Type: research