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Using long-term co-cultures of reactive astrocytes and human motor neurons, Zhou and colleagues show that reactive astrocytes, regardless of their genetic makeup, are toxic to motor neurons and induce neuronal loss, neurite shrinkage, and axonal and cytoplasmic protein inclusions. Reactive astrocytes promote neuronal protein aggregation partly through enhanced TGF-β1 signaling, which activates mTOR pathway and impairs autophagy in motor neurons.
In this article, Arantxa Tabernero and colleagues show that a short region of Connexin43 exerts an important anti-tumor effect in patient-derived glioblastoma models that includes the impairment of glioma stem cell migration and invasion. This peptide targets important proteins for glioblastoma, such as Src, FAK, and PTEN, highlighting its relevance for therapeutic development against this incurable disease.
Perestrelo et al. show an image-analysis methodology coupled with a machine-learning platform to analyze and quantify pluripotency with high accuracy in different contexts. Requiring low user input, this software allows the pluripotency evaluation of large low-magnification images, with colony visualization and automated data analysis comparison among experiments.
The International Stem Cell Initiative organized a conference to review current understanding of the detection, origins, and consequences of genetic and epigenetic variants that arise in cultures of human pluripotent stem cells. This report provides an overview of the discussions and a recommendation to form an advisory group to help reach an international consensus on risk assessment for clinical applications.
In this article, Caffrey, Wade-Martins, and colleagues show extended maturation of dopaminergic neuronal cultures gives expression of six adult tau isoforms displaying MAPT haplotype-specific differences in expression. Further, knocking down adult tau protein variants alters axonal transport velocities in mature iPSC-derived dopaminergic neuronal cultures, linking haplotype-specific MAPT expression with a biologically functional outcome relevant for PD.
Liu, Miao, and colleagues explore the chromosome dynamics during reprogramming of porcine fibroblasts after SCNT. By applying MNase-seq with low cell input, which is particularly important for scarce biological samples, they reveal a dynamic reorganization of nucleosomes during reprogramming.
In this article, Grompe and colleagues show that the cholangiocyte compartment of adult liver is heterogeneous. Their work shows conclusively that they differ in their clonogenic potential in the “Clevers” organoid assay and that they have a distinct gene expression profile.
Karunanithi and colleagues demonstrate that the RBP4-STRA6 pathway is critical for colon cancer stem cell (CSC) maintenance. Downregulating STRA6 or RBP4 in colon cancer cells decreases CSC population and self-renewal. Increased levels of CSC markers and tumor growth in response to high-fat feeding are abrogated upon STRA6 silencing. The RBP4-STRA6 pathway may provide a link between high-fat feeding and colon carcinogenesis.
Jang and colleagues show that SIRT1 downregulation in hESCs decreased the levels of DNA repair enzymes such as MSH2, MSH6, and APEX1 and increased DNA damage (in both SSBs and DSBs). The authors also demonstrate that SIRT1 inhibition induced massive cell death, caused at least partially by DNA damage-mediated p53 activation. Thus, SIRT1 contributes to genome stability and survival of hESCs.
Martinot et al. report that FXRα controls the fate of undifferentiated spermatogonia.
In this article, Zhao and colleagues report a novel technology delivering directional electric currents which mobilizes and guides human neural stem cells through the brain in vivo, demonstrating an effective and safe approach to facilitate stem cell therapy, with significant implications for a wide range of brain diseases.
Disruption of redox homeostasis can affect stem cell behavior. In the Drosophila testis, high ROS induced by altered Keap1/Nrf2 signaling decrease GSC number by promoting GSC differentiation via the activation of EGFR signaling. By contrast, testes with low ROS show an overgrowth of GSC-like cells. These findings suggest the importance of redox homeostasis in the Drosophila testis GSC maintenance.
In this article, Smith and colleagues investigate the character of embryonic stem cells that initiate differentiation in the absence of exogenous cytokines. They find that cells that have extinguished self-renewal are responsive to inductive cues for germline and somatic lineage specification. They present evidence that autocrine NODAL signaling potentiates the formative transition to multi-lineage competence.
The mechanism of mammalian hair cell development is not fully understood. In this article, Wei-Qiang Gao and colleagues show that inactivation of STAT3 signaling impairs mammalian cochlear hair cell differentiation, by influencing asymmetric and symmetric cell division modes. The STAT3 pathway is downstream of the Notch signaling for the regulation of hair cell production.
In this article, Yan and colleagues show that BACE1 is required for the proper formation of the granule cell layer. BACE1 deficiency in mice induces retention of clustered doublecortin-positive neuroblasts in the subpial zone (SPZ) and marginal zone (MZ). Upregulation of reelin in Cajal-Retzius cells likely causes timely migration of neuroblasts in SPZ/MZ to form Prox1-positive granule cells.
Yazawa and colleagues report cyclin-dependent kinase 5 (CDK5) as a regulator of CaV1.2 channels in cardiomyocytes and a molecular therapeutic target for Timothy syndrome. This study provides insights into the regulation of cardiac calcium channels and the development of future therapeutics for Timothy syndrome patients.
Nuclear factor erythroid-derived 2 (NFE2) has been historically associated with megakaryocyte maturation and platelet production. In this article, Bonnet and colleagues show that NFE2 regulates both human HSC self-renewal and T cell differentiation by modulating NOTCH1 activation via the regulation of γ-secretase components.
CpG methylation is established globally in adult immature oocytes and remains stable during maturation. Non-CpG methylation undergoes a genome-wide, generalized remodeling through the final stage of maturation, with the net overall result being accumulation of methylation as oocytes mature.
Pinto-do-Ó and colleagues establish a role for HES5 in instructing cardiac versus primitive erythroid fate. Hes5 depletion enhances primitive erythropoiesis, whereas a stage-specific overexpression favors cardiac specification in mESCs. Progression of differentiation to contracting cardiomyocytes depends on Hes5 downregulation. This requirement for transient Hes5 activity for proper cardiogenesis correlates with the expression pattern observed in the mouse embryo nascent mesoderm.
In this article, García-Verdugo and colleagues show that a subpopulation of quiescent B cells in the ventricular-subventricular zone of the brain show a unique nuclear envelope structure identified as nuclear envelope-limited chromatin sheets (ELCS). This structure, which appears in embryonic stages, represents a nuclear compartment with specific chromatin and epigenetic modifications.