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In this article, Heath, van Delft, and colleagues show that mitochondrial apoptosis limits OKSM-mediated reprogramming of MEFs. Not only is reprogramming of MEFs lacking the two essential mediators of mitochondrial apoptosis, BAK and BAX, significantly enhanced in the presence of MYC, but reprogramming in these conditions does not compromise genome integrity.
Sterneckert and colleagues generate isogenic FUS-eGFP reporter iPSCs that enable the identification of stress granule (SG) phenotypes specifically induced by the ALS mutation FUS P525L. Compound screening shows that modulation of the PI3K/AKT/mTOR pathway regulating autophagy ameliorates SG phenotypes. A second screen identifies similarly acting brain-penetrant US FDA-approved drugs that could be repurposed to treat ALS.
H. Wang et al. identify MEIS1 as an essential regulator of early hematopoiesis and megakaryopoiesis from hPSCs in a stage-specific manner. This can be potentially manipulated for large-scale generation of HPCs or platelets from hPSCs for therapeutic applications in regenerative medicine.
In this article, Sridharan and colleagues perform proteomic characterization of the heterochromatin protein 1 (HP1) family in reprogramming and pluripotency. Depletion of HP1γ or its interacting partner SENP7, which anchors it to heterochromatin, increased iPSC generation. In pluripotent cells, HP1γ is highly nucleoplasmic and enriched with histone H3.3. HP1γ interacts with OCT4 and DPPA4 independent of HP1α, HP1β, and H3K9 methylation. HP1α and HP1γ differ in association with specific components of chromatin-modifying complexes such as DPY30.
In this article, Liangxue Lai and colleagues show that nullification of the XIST gene in donor cells can normalize aberrant gene expression in cloned embryos and result in high cloning efficiency in pigs.
In this article, García-León JA and colleagues demonstrate the generation of functional oligodendrocytes (OLs) from human pluripotent stem cells in a rapid and efficient manner by the single overexpression of SOX10. Generated OLs resemble primary OLs at the transcriptome level and can myelinate neurons both in vivo and in vitro. Neuron-OL co-cultures, adapted to high-throughput screening formats, responded to drugs affecting myelination.
In this study, examination of the satellite cell microenvironment in vivo revealed that these cells are encapsulated by LMα2–5. We find that reconstitution of the satellite cell niche with recombinant LM-E8 fragments promotes the proliferation and maintains satellite cells in an undifferentiated state.
In this article, Gupta and colleagues describe a robust protocol to derive spinal dorsal sensory interneurons from human pluripotent stem cells using the sequential addition of RA and BMP4. They find that neural progenitors must be in the correct competence state to respond to RA/BMP4 as dorsalizing signals. This competence state changes over time and determines the efficiency of the protocol.
In this report, Mielenz, Winner, and colleagues show a novel impact of Efhd2 on survival and integration of adult-born hippocampal neurons. This is of particular significance since EFHD2 regulates cytoskeletal transport and synaptic plasticity and since levels of pathological TAU are increased in Efhd2 knockout mice.
In this article, Garbuzov and colleagues devise a new strategy for isolating pure populations of GFRα1+ and GFRα1– undifferentiated spermatogonia from adult testis of TertTomato reporter mice based on expression of telomerase and GFRα1. Transcriptional profiling showed a remarkable similarity between GFRα1+ and GFRα1– cells, and both populations showed elevated stem cell activity by transplantation.
In this article, Maki and Takahashi report that the internalization of exogenous α-synuclein fibrils in oligodendrocyte precursor cells triggers misfolding and accumulation of endogenous α-synuclein via seeding mechanisms, which may eventually lead to neurodegeneration and myelin disruption in multiple system atrophy by compromising the oligodendroglial function of neuronal support and myelination.
Vereide and colleagues identify a means to induce and maintain human arterial endothelial precursors (eAEPs) in culture by using two transcription factors, MYCN and SOX17. Although the eAEPs facilitate a range of human arterial studies, in this study the authors examine the propensities of the precursors to transition to a mesenchymal state, a change associated with vascular disease.
In this article Kurtz, Seltmann and colleagues propose a standard nomenclature and registry for human pluripotent stem cells. The nomenclature is based on fixed name elements and provides a unique identifier for PSC lines suitable for referencing over diverse data sources, registries, publications, and cell banks. Rigorous application is needed to reduce risks from misidentification and false referencing of lines and data.
Pearson and colleagues demonstrate that transplanted cone photoreceptors can both undergo incorporation into the host neural retina and engage in cytoplasmic material transfer with host rod and cone photoreceptors. They show that the host environment plays a crucial role in determining the relative contributions of these two mechanisms to transplantation outcome.
By developing and characterizing new fluorescent probes enabling fast, reversible, and ratiometric reaction with glutathione, Jeong et al. reveal considerable dynamics and heterogeneity in glutathione levels in living stem cells in response to environmental stress and also show that high glutathione levels are required for maintaining stemness of murine embryonic stem cells or therapeutic potency of mesenchymal stem cells.
In this article, Pang and colleagues demonstrate a p53-dependent HSPC proliferation regulation in mice deficient for the Fanca gene in the Fanconi anemia (FA) pathway. They show that the p53 cell-cycle function is specifically required for the regulation of FA HSC proliferation. These results suggest that overactive p53 may represent a compensatory checkpoint mechanism for FA HSC proliferation.
Crooks and colleagues demonstrated a previously underappreciated functional and molecular heterogeneity in mesenchyme generated from human pluripotent stem cells. Two mesenchymal subsets were distinguished by the reciprocal expression of CD146, CD73, and CD140a. CD146hiCD73hi mesenchyme supported self-renewing hematopoietic stem and progenitor cells (HSPCs), expressed markers of the HSPC niche, and shared a similar molecular signature with primary human adult pericytes.
In this article, Saha and colleagues describe a workflow for isolation of hPSC clones containing scarless, HDR-mediated, genome edits without the use of FACS or high-throughput sequencing technologies. They demonstrate that transient expression of a puromycin-resistance gene, from a non-integrated CRISPR/Cas9 plasmid, enables stringent selection for clones precisely edited with a single-stranded donor DNA template.
In this article, Huang and colleagues demonstrate that niche hypoxia promotes symmetric self-renewal proliferation and migration of PGC-like CD49f+AP+GSCs through IGF-IR regulation. Using a serum-free culture system, the crosstalk between IGF-1R and CXCR4 signaling was discovered. This work demonstrated that embryonic hypoxia synergistically cooperated with IGF-1R signaling to regulate the symmetric self-renewal and migration of PGC-like GSCs through a HIF-2α–OCT4/CXCR4 loop.
del Barco Barrantes and colleagues use genetically modified mice to identify p38α as a key regulator of the fate of luminal progenitor cells of the mammary gland, which impinges on the ability of these cells to initiate tumors.