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Cell Stem Cell

Guillermo C Rivera-Gonzalez, Brett A Shook, Johanna Andrae, Brandon Holtrup, Katherine Bollag, Christer Betsholtz, Matthew S Rodeheffer, Valerie Horsley
Tissue growth and maintenance requires stem cell populations that self-renew, proliferate, and differentiate. Maintenance of white adipose tissue (WAT) requires the proliferation and differentiation of adipocyte stem cells (ASCs) to form postmitotic, lipid-filled mature adipocytes. Here we use the dynamic adipogenic program that occurs during hair growth to uncover an unrecognized regulator of ASC self-renewal and proliferation, PDGFA, which activates AKT signaling to drive and maintain the adipogenic program in the skin...
October 1, 2016: Cell Stem Cell
Anna E Beaudin, Scott W Boyer, Jessica Perez-Cunningham, Gloria E Hernandez, S Christopher Derderian, Chethan Jujjavarapu, Eric Aaserude, Tippi MacKenzie, E Camilla Forsberg
The generation of distinct hematopoietic cell types, including tissue-resident immune cells, distinguishes fetal from adult hematopoiesis. However, the mechanisms underlying differential cell production to generate a layered immune system during hematopoietic development are unclear. Using an irreversible lineage-tracing model, we identify a definitive hematopoietic stem cell (HSC) that supports long-term multilineage reconstitution upon transplantation into adult recipients but does not persist into adulthood in situ...
September 15, 2016: Cell Stem Cell
Noemi A Zambetti, Zhen Ping, Si Chen, Keane J G Kenswil, Maria A Mylona, Mathijs A Sanders, Remco M Hoogenboezem, Eric M J Bindels, Maria N Adisty, Paulina M H Van Strien, Cindy S van der Leije, Theresia M Westers, Eline M P Cremers, Chiara Milanese, Pier G Mastroberardino, Johannes P T M van Leeuwen, Bram C J van der Eerden, Ivo P Touw, Taco W Kuijpers, Roland Kanaar, Arjan A van de Loosdrecht, Thomas Vogl, Marc H G P Raaijmakers
Mesenchymal niche cells may drive tissue failure and malignant transformation in the hematopoietic system, but the underlying molecular mechanisms and relevance to human disease remain poorly defined. Here, we show that perturbation of mesenchymal cells in a mouse model of the pre-leukemic disorder Shwachman-Diamond syndrome (SDS) induces mitochondrial dysfunction, oxidative stress, and activation of DNA damage responses in hematopoietic stem and progenitor cells. Massive parallel RNA sequencing of highly purified mesenchymal cells in the SDS mouse model and a range of human pre-leukemic syndromes identified p53-S100A8/9-TLR inflammatory signaling as a common driving mechanism of genotoxic stress...
September 10, 2016: Cell Stem Cell
Tito Panciera, Luca Azzolin, Atsushi Fujimura, Daniele Di Biagio, Chiara Frasson, Silvia Bresolin, Sandra Soligo, Giuseppe Basso, Silvio Bicciato, Antonio Rosato, Michelangelo Cordenonsi, Stefano Piccolo
The ability to induce autologous tissue-specific stem cells in culture could have a variety of applications in regenerative medicine and disease modeling. Here we show that transient expression of exogenous YAP or its closely related paralogue TAZ in primary differentiated mouse cells can induce conversion to a tissue-specific stem/progenitor cell state. Differentiated mammary gland, neuronal, and pancreatic exocrine cells, identified using a combination of cell sorting and lineage tracing approaches, efficiently convert to proliferating cells with properties of stem/progenitor cells of their respective tissues after YAP induction...
September 9, 2016: Cell Stem Cell
Alpaslan Tasdogan, Suresh Kumar, Gabriele Allies, Julia Bausinger, Franziska Beckel, Helmut Hofemeister, Medhanie Mulaw, Vikas Madan, Karin Scharfetter-Kochanek, Michaela Feuring-Buske, Konstanze Doehner, Günter Speit, A Francis Stewart, Hans Joerg Fehling
Mouse mutants with an impaired DNA damage response frequently exhibit a set of remarkably similar defects in the HSPC compartment that are of largely unknown molecular basis. Using Mixed-Lineage-Leukemia-5 (Mll5)-deficient mice as prototypical examples, we have identified a mechanistic pathway linking DNA damage and HSPC malfunction. We show that Mll5 deficiency results in accumulation of DNA damage and reactive oxygen species (ROS) in HSPCs. Reduction of ROS efficiently reverses hematopoietic defects, establishing ROS as a major cause of impaired HSPC function...
September 7, 2016: Cell Stem Cell
Matthew S Alexander, Anete Rozkalne, Alessandro Colletta, Janelle M Spinazzola, Samuel Johnson, Fedik Rahimov, Hui Meng, Michael W Lawlor, Elicia Estrella, Louis M Kunkel, Emanuela Gussoni
Cell-surface markers for prospective isolation of stem cells from human skeletal muscle have been difficult to identify. Such markers would be powerful tools for studying satellite cell function during homeostasis and in pathogenesis of diseases such as muscular dystrophies. In this study, we show that the tetraspanin KAI/CD82 is an excellent marker for prospectively isolating stem cells from human fetal and adult skeletal muscle. Human CD82(+) muscle cells robustly engraft into a mouse model of muscular dystrophy...
September 7, 2016: Cell Stem Cell
Rafael Kramann, Claudia Goettsch, Janewit Wongboonsin, Hiroshi Iwata, Rebekka K Schneider, Christoph Kuppe, Nadine Kaesler, Monica Chang-Panesso, Flavia G Machado, Susannah Gratwohl, Kaushal Madhurima, Joshua D Hutcheson, Sanjay Jain, Elena Aikawa, Benjamin D Humphreys
Mesenchymal stem cell (MSC)-like cells reside in the vascular wall, but their role in vascular regeneration and disease is poorly understood. Here, we show that Gli1(+) cells located in the arterial adventitia are progenitors of vascular smooth muscle cells and contribute to neointima formation and repair after acute injury to the femoral artery. Genetic fate tracing indicates that adventitial Gli1(+) MSC-like cells migrate into the media and neointima during athero- and arteriosclerosis in ApoE(-/-) mice with chronic kidney disease...
August 29, 2016: Cell Stem Cell
Chung-Han Hsieh, Atossa Shaltouki, Ashley E Gonzalez, Alexandre Bettencourt da Cruz, Lena F Burbulla, Erica St Lawrence, Birgitt Schüle, Dimitri Krainc, Theo D Palmer, Xinnan Wang
Mitochondrial movements are tightly controlled to maintain energy homeostasis and prevent oxidative stress. Miro is an outer mitochondrial membrane protein that anchors mitochondria to microtubule motors and is removed to stop mitochondrial motility as an early step in the clearance of dysfunctional mitochondria. Here, using human induced pluripotent stem cell (iPSC)-derived neurons and other complementary models, we build on a previous connection of Parkinson's disease (PD)-linked PINK1 and Parkin to Miro by showing that a third PD-related protein, LRRK2, promotes Miro removal by forming a complex with Miro...
August 25, 2016: Cell Stem Cell
Leslie A Crews, Larisa Balaian, Nathaniel P Delos Santos, Heather S Leu, Angela C Court, Elisa Lazzari, Anil Sadarangani, Maria A Zipeto, James J La Clair, Reymundo Villa, Anna Kulidjian, Rainer Storb, Sheldon R Morris, Edward D Ball, Michael D Burkart, Catriona H M Jamieson
Age-related human hematopoietic stem cell (HSC) exhaustion and myeloid-lineage skewing promote oncogenic transformation of hematopoietic progenitor cells into therapy-resistant leukemia stem cells (LSCs) in secondary acute myeloid leukemia (AML). While acquisition of clonal DNA mutations has been linked to increased rates of secondary AML for individuals older than 60 years, the contribution of RNA processing alterations to human hematopoietic stem and progenitor aging and LSC generation remains unclear. Comprehensive RNA sequencing and splice-isoform-specific PCR uncovered characteristic RNA splice isoform expression patterns that distinguished normal young and aged human stem and progenitor cells (HSPCs) from malignant myelodysplastic syndrome (MDS) and AML progenitors...
August 25, 2016: Cell Stem Cell
Beatriz Aranda-Orgilles, Ricardo Saldaña-Meyer, Eric Wang, Eirini Trompouki, Anne Fassl, Stephanie Lau, Jasper Mullenders, Pedro P Rocha, Ramya Raviram, María Guillamot, María Sánchez-Díaz, Kun Wang, Clarisse Kayembe, Nan Zhang, Leonela Amoasii, Avik Choudhuri, Jane A Skok, Markus Schober, Danny Reinberg, Piotr Sicinski, Heinrich Schrewe, Aristotelis Tsirigos, Leonard I Zon, Iannis Aifantis
Hematopoietic-specific transcription factors require coactivators to communicate with the general transcription machinery and establish transcriptional programs that maintain hematopoietic stem cell (HSC) self-renewal, promote differentiation, and prevent malignant transformation. Mediator is a large coactivator complex that bridges enhancer-localized transcription factors with promoters, but little is known about Mediator function in adult stem cell self-renewal and differentiation. We show that MED12, a member of the Mediator kinase module, is an essential regulator of HSC homeostasis, as in vivo deletion of Med12 causes rapid bone marrow aplasia leading to acute lethality...
August 24, 2016: Cell Stem Cell
Hongda Li, Laura Saucedo-Cuevas, Jose A Regla-Nava, Guoliang Chai, Nicholas Sheets, William Tang, Alexey V Terskikh, Sujan Shresta, Joseph G Gleeson
Zika virus (ZIKV)-related neuropathology is an important global health concern. Several studies have shown that ZIKV can infect neural stem cells in the developing brain, but infection in the adult brain has not been examined. Two areas in the adult mouse brain contain neural stem cells: the subventricular zone of the anterior forebrain and the subgranular zone of the hippocampus. Here, using 6-week-old mice triply deficient in interferon regulatory factor (IRF) as a model, we show that blood-borne ZIKV administration can lead to pronounced evidence of ZIKV infection in these adult neural stem cells, leading to cell death and reduced proliferation...
August 17, 2016: Cell Stem Cell
Chiara Rolando, Andrea Erni, Alice Grison, Robert Beattie, Anna Engler, Paul J Gokhale, Marta Milo, Thomas Wegleiter, Sebastian Jessberger, Verdon Taylor
Adult neural stem cells (NSCs) are defined by their inherent capacity to self-renew and give rise to neurons, astrocytes, and oligodendrocytes. In vivo, however, hippocampal NSCs do not generate oligodendrocytes for reasons that have remained enigmatic. Here, we report that deletion of Drosha in adult dentate gyrus NSCs activates oligodendrogenesis and reduces neurogenesis at the expense of gliogenesis. We further find that Drosha directly targets NFIB to repress its expression independently of Dicer and microRNAs...
August 15, 2016: Cell Stem Cell
Qiming Liang, Zhifei Luo, Jianxiong Zeng, Weiqiang Chen, Suan-Sin Foo, Shin-Ae Lee, Jianning Ge, Su Wang, Steven A Goldman, Berislav V Zlokovic, Zhen Zhao, Jae U Jung
The current widespread outbreak of Zika virus (ZIKV) infection has been linked to severe clinical birth defects, particularly microcephaly, warranting urgent study of the molecular mechanisms underlying ZIKV pathogenesis. Akt-mTOR signaling is one of the key cellular pathways essential for brain development and autophagy regulation. Here, we show that ZIKV infection of human fetal neural stem cells (fNSCs) causes inhibition of the Akt-mTOR pathway, leading to defective neurogenesis and aberrant activation of autophagy...
August 9, 2016: Cell Stem Cell
Stefano Di Talia, Kenneth D Poss
For tissue regeneration researchers, seeing is believing. Here, we consider advances in genetic tools, imaging platforms, and quantification capabilities that are turning previously unattainable goals, like in toto capture of cellular and subcellular behaviors in regenerating tissues, into reality.
October 6, 2016: Cell Stem Cell
Armin Blesch
Beyond impaired motor and sensory function, neuropathic pain and loss of bladder control caused by spinal cord injuries (SCIs) can severely affect quality of life. In this issue of Cell Stem Cell, Fandel et al. (2016) show that transplanted human ESC-derived cells biased to produce inhibitory interneurons significantly improve pain and bladder function in rodent SCI models.
October 6, 2016: Cell Stem Cell
James C Chen, Angela M Christiano
Mammalian skin is a complex and heterogeneous tissue with several distinct compartments and stem cell populations. Joost et al. (2016) now use single-cell RNaseq to comprehensively reconstruct this complexity, revealing spatial and pseudotemporal differences between transcriptional programs in distinct compartments and a common basal program in skin stem cell populations.
October 6, 2016: Cell Stem Cell
Barbara Mlody, Alessandro Prigione
Glycolysis is an essential component of cellular metabolism associated with pluripotent stem cells (PSCs). Two new papers, one by Gu et al. (2016) in this issue of Cell Stem Cell and one by Zhang et al. (2016) in Cell Reports, demonstrate that glycolytic flux is dynamically increased in human primed PSCs upon feeder-free cultivation or conversion into the naive state.
October 6, 2016: Cell Stem Cell
Jessica A Lehoczky
Digit tip regeneration following amputation is an innate response in some mammals, including mice. In this issue of Cell Stem Cell, Johnston et al. (2016) show that Schwann cell precursors are necessary for this process and can rescue regeneration in denervated digit tips through secretion of pro-regenerative factors including OSM and PDGF-AA.
October 6, 2016: Cell Stem Cell
Ying Wang, George L Sen
In this issue of Cell Stem Cell, Rinaldi et al. (2016) find an unexpected role for the de novo DNA methyltransferases Dnmt3a and Dnmt3b in the regulation of enhancers. Their findings provide new insight into how regulation of enhancer activity through DNA methylation can have dramatic consequences on epidermal stem cell fate decisions.
October 6, 2016: Cell Stem Cell
Thomas M Fandel, Alpa Trivedi, Cory R Nicholas, Haoqian Zhang, Jiadong Chen, Aida F Martinez, Linda J Noble-Haeusslein, Arnold R Kriegstein
Neuropathic pain and bladder dysfunction represent significant quality-of-life issues for many spinal cord injury patients. Loss of GABAergic tone in the injured spinal cord may contribute to the emergence of these symptoms. Previous studies have shown that transplantation of rodent inhibitory interneuron precursors from the medial ganglionic eminence (MGE) enhances GABAergic signaling in the brain and spinal cord. Here we look at whether transplanted MGE-like cells derived from human embryonic stem cells (hESC-MGEs) can mitigate the pathological effects of spinal cord injury...
October 6, 2016: Cell Stem Cell
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