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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.
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.
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, 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.
(Stem Cell Reports 5, 918–931; November 10, 2015)
(Stem Cell Reports 8, 634-647; March 14, 2017)
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.
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.
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.
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.
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.
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.
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.
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 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.
Ectopic expression of Dnmt3b could rescue DNA methylation level in repetitive sequences of hypomethylated AG-haESCs, suppress high incidence of self-diploidization, and promote developmental potential of SC embryos, and most SC mice could survive into adulthood.
Yuan and colleagues show that primary cilia are deficient in obese adipose-derived mesenchymal stem cells (ASCs). Impaired cilia render ASCs dysfunctional, accounting possibly for defective adipogenesis, adipocyte hypertrophy, hypoxia, and deregulated immunomodulation. Inhibition of Aurora A/HDAC6 rescues obese cilia, suggestive of an alternative strategy to combat obesity and its associated diseases.
In this article, Shirley ShiDu Yan and colleagues show that human pluripotent stem cell-derived astrocytes effectively rescue defects in neurogenesis of dopaminergic neurons with mitochondrial respiratory chain disruption. Co-culture with astrocytes restored mitochondrial functions and dynamics in dopaminergic neurons insulted by mitochondrial toxins. These results provide evidence of astroglia in maintaining mitochondrial development and bioenergetics during dopaminergic neuronal differentiation.
Ngondo et al. report that Ago2 is required for the extra-embryonic endoderm (ExEn) differentiation in vitro. While AGO2 is dispensable for proper embryo formation, its deletion in mESCs causes a decreased induction of ExEn genes, leading to an impaired differentiation. This defect is cell autonomous and involves AGO2 small-RNA binding capacity.
In this article, Enikolopov and colleagues describe a method for triple S-phase labeling of stem cells, with an additional channel used to phenotype the cells or to add the fourth marker of cell division. They demonstrate the method's utility for birth dating multiple stem cell populations and for revealing patterns of stem cell division in the brain, testis, and intestine.