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An Ultraconserved Element Containing lncRNA Preserves Transcriptional Dynamics and Maintains ESC Self-Renewal

Thu, 02/15/2018 - 00:00
In this article Fico, Minchiotti, and colleagues identify an ultraconserved element containing long non-coding RNA, named T-UCstem1, in embryonic stem cells (ESCs) and provide evidence that it regulates cell-cycle progression by modulating cytoplasmic miR-9 levels and preserves ESC identity and self-renewal by stabilizing polycomb repressive complex 2 (PRC2) on bivalent domains.

Mitochondrial Dysfunctions Contribute to Hypertrophic Cardiomyopathy in Patient iPSC-Derived Cardiomyocytes with MT-RNR2 Mutation

Thu, 02/15/2018 - 00:00
In this article, Yan Q, Liu Z, Huang W, and colleagues show that patient-specific iPSCs as well as their derived cardiomyocytes carrying the m.2336T>C mutation in MT-RNR2 were generated to understand the pathogenic mechanism of maternally inherited HCM. MT-RNR2 mutation resulted in mitochondrial dysfunctions and ultrastructure defects, which induced abnormal Ca2+ homeostasis, then HCM-specific cellular and electrophysiological characteristics in iPSC-CMs.

Neurons Generated by Mouse ESCs with Hippocampal or Cortical Identity Display Distinct Projection Patterns When Co-transplanted in the Adult Brain

Thu, 02/15/2018 - 00:00
In this article, Terrigno and colleagues show that Wnt and BMB signaling control the differentiation of mouse ESCs toward isocortical or hippocampal identity in vitro. The two types of cells contact different regions when transplanted in adult brain. Photothrombotic lesion favors neurite elongation of cortical transplanted cells, which can improve the motor performance after ischemic damage of motor cortex.

HOXB4 Promotes Hemogenic Endothelium Formation without Perturbing Endothelial Cell Development

Thu, 02/15/2018 - 00:00
In this article, Klump and colleagues demonstrate that the human homeotic selector protein HOXB4 promotes ESC-derived hematopoiesis by inducing hemogenic endothelium formation, in vitro. It propels hematopoietic specification by upregulating the transcription of genes essential for hematopoietic development, such as those encoding members of the so-called heptad transcription factors.

RAS Regulates the Transition from Naive to Primed Pluripotent Stem Cells

Thu, 02/15/2018 - 00:00
Altshuler et al. report that RAS activation positively regulated key processes of naive-primed transition of mouse embryonic stem cells, including changes in metabolism, chromatin remodeling, and the switch in CADHERIN expression. Pharmacological inhibition of RAS attenuated cellular priming, suggesting that RAS inhibition may be potentially useful for converting human cells into ground state and for efficient somatic cellular reprogramming.

Ihor Lemischka (1953-2017)

Tue, 02/13/2018 - 00:00
Ihor Lemischka, PhD, Professor at the Icahn School of Medicine at Mount Sinai in New York died, much too young, from a stroke early in December 2017. Ihor will be remembered for his great sense of humor and his pioneering work on embryonic and hematopoietic stem cells. Throughout his career he showed an unwavering desire to understand the behavior of stem cells from a mechanistic, biochemical point of view. He wanted to know how cell fate decisions were made. In his quest he applied a variety of approaches from transistor models used in electronics to large gene expression and proteomics datasets from various laboratories, including his own.

ADAM8 Is an Antigen of Tyrosine Kinase Inhibitor-Resistant Chronic Myeloid Leukemia Cells Identified by Patient-Derived Induced Pluripotent Stem Cells

Thu, 02/08/2018 - 00:00
The paucity and heterogeneity of CML stem cells are obstacles for analyses. In our study, a model of CML stem cells derived from CML-iPSCs identified ADAM8 as an antigen of TKI-resistant cells. In CML patients, ADAM8+ cells showed TKI resistance and residual CML cells after TKIs-treatment were concentrated in ADAM8+ population, suggesting that ADAM8 is a marker of TKI-resistant CML cells.

Low Resting Membrane Potential and Low Inward Rectifier Potassium Currents Are Not Inherent Features of hiPSC-Derived Cardiomyocytes

Thu, 02/08/2018 - 00:00
We show here that RMP is systematically underestimated in patch-clamped hiPSC-CMs and, in the 3D EHT format, reaches physiological values of human adult CMs when measured by sharp microelectrodes. This corresponds with IK1 currents as large as in human adult CMs. In human adult preparations, repolarization fraction was more useful than APD and RMP to classify action potentials as atrial or ventricular like.

Generation of Functioning Nephrons by Implanting Human Pluripotent Stem Cell-Derived Kidney Progenitors

Thu, 02/08/2018 - 00:00
Kimber and colleagues show that pluripotent stem cell-derived kidney progenitors implanted subcutaneously generate vascularized glomeruli including podocytes with slit diaphragms and mature glomerular basement membranes indicative of functioning glomeruli. Human cells contributed to the vasculature, and the glomeruli were able to filter low-molecular-weight dextran injected intravenously, which appeared in some tubules.

The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53

Thu, 02/08/2018 - 00:00
In this article, Pisconti et al. use an unbiased approach to show that the transcriptional program that drives myoblast cell fate transitions is directly regulated by the nature of the surrounding niche. The authors identify p53 as a niche-induced transcriptional regulator that increases in a subset of myoblasts upon cell-cycle exit, promoting quiescence at the expense of differentiation.

Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids

Thu, 02/08/2018 - 00:00
In this article, Takebe, Taniguchi, and colleagues derived a unique population of CDX2+ posterior endoderm progenitors (PGECs) from human pluripotent stem cells that are highly expandable and storable in a chemically defined condition. CDX2+ endoderm progenitors can form multiple endodermal organoids. Transplantation of human liver bud organoids from robustly propagated PGECs rescued lethal liver failure of immunodeficient mice.

A Non-apoptotic Function of MCL-1 in Promoting Pluripotency and Modulating Mitochondrial Dynamics in Stem Cells

Thu, 02/08/2018 - 00:00
Gama and colleagues show that MCL-1 regulates mitochondrial network morphology in human pluripotent stem cells. MCL-1 downregulation resulted in loss of OCT4 and NANOG and an elongated mitochondrial network. MCL-1 associates with mitochondrial dynamics regulators; this association is disrupted by an MCL-1 small-molecule inhibitor. The results provide mechanistic insight into the connection between apoptosis, mitochondrial dynamics, and pluripotency.

Testicular Architecture Is Critical for Mediation of Retinoic Acid Responsiveness by Undifferentiated Spermatogonial Subtypes in the Mouse

Thu, 02/01/2018 - 00:00
Lord et al. have demonstrated that, contrary to previous assumptions, spermatogonial stem cells do express a functional complement of retinoic acid and retinoid X receptors (RARs/RXRs) and rely on protection from an undisturbed niche microenvironment to prevent loss of the spermatogenic reservoir to RA-induced differentiation.

Comparison of Non-human Primate versus Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Treatment of Myocardial Infarction

Thu, 02/01/2018 - 00:00
In this article, Wu and colleagues demonstrate the therapeutic similarities of non-human primate iPSC-CMs and human iPSC-CMs to treat myocardial infarction by improving cardiac function and attenuating myocardial remodeling in a rodent myocardial infarction model. Mechanisms of iPSC-CM therapy include promotion of cell survival, angiogenesis, and inhibition of hypertrophy and fibrosis.

In Vitro Modeling of Human Germ Cell Development Using Pluripotent Stem Cells

Thu, 02/01/2018 - 00:00
In this article, Wang and colleagues established a feeder- and xeno-free system to robustly induce human pluripotent stem cells (PSCs) into spermatogonia-like cells. This chemically defined induction protocol faithfully recapitulated the features of compromised germ cell development of PSCs with NANOS3 deficiency or iPSC lines established from patients with non-obstructive azoospermia.

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