Identification and Successful Negotiation of a Metabolic Checkpoint in Direct Neuronal Reprogramming
Bhaskar Chanda Stem Cell By imaging cell fate conversion over time, Gascón, Murenu, and colleagues find that high levels of oxidative stress prevent successful direct neuronal reprogramming, instead causing extensive cell death. They identify inhibitors of ferroptosis, antioxidants, and Bcl-2 as key metabolic agents in improving generation of iNs from a range of somatic cells and in vivo after brain injury.
Bhaskar Chanda Stem Cell In this article, Greber and colleagues reveal signaling principles that underlie directed differentiation of human ESCs into cardiomyocytes. The authors show that BMP and WNT pathways promote cardiac induction through sequential and dose-dependent suppression of repressive regulators that otherwise drive differentiation into alternate lineages.
Bhaskar Chanda Stem Cell Mascetti and Pedersen show that stage-matching of human pluripotent cells to gastrula-stage mouse embryos overcomes barriers to chimerism, allowing efficient interspecies chimera formation with widespread cell dispersal and tissue-specific differentiation. These findings provide in vivo functional validation of hPSC pluripotency.
Bhaskar Chanda Stem Cell Ji et al. map the chromosome organizational structures that underlie gene regulation in human naive and primed pluripotent cells. Their framework of cohesin-associated CTCF loops, and the cohesin-associated enhancer-promoter loops within them, provides a reference map for future interrogation of regulatory interactions.
Intravital Imaging Reveals Ghost Fibers as Architectural Units Guiding Myogenic Progenitors during Regeneration
Bhaskar Chanda Stem Cell Webster et al. show that the basal lamina remnants of degenerated skeletal muscle fibers, “ghost fibers,” are architectural units containing and guiding muscle progenitors during injury-induced regeneration in live mice. Their work identifies ghost fibers as the cellular mechanism regulating organization and number of regenerated fibers for proportional regeneration.
Bhaskar Chanda Stem Cell The complex gene regulatory networks that control stem cell behavior are only partially understood. Sanchez et al. describe an unbiased in vivo RNAi screen and provide a formative dissection of the gene pathways required for germline stem cell development.
Genomic Instability in Human Pluripotent Stem Cells Arises from Replicative Stress and Chromosome Condensation Defects
Bhaskar Chanda Stem Cell Lamm et al. identify a mechanism leading to the ongoing chromosomal instability observed in hPSCs harboring recurrent aneuplodies and which may induce instability in diploid hPSCs. They find that decreased SRF levels cause cytoskeletal impairments that perturb DNA replication and chromosomal condensation, resulting in chromosome segregation errors and genomic instability.
Regulation of Skeletal Muscle Stem Cell Quiescence by Suv4-20h1-Dependent Facultative Heterochromatin Formation
Bhaskar Chanda Stem Cell Boonsanay et al. show that Suv4-20h1 dynamically regulates muscle stem cell quiescence by regulating facultative heterochromatin formation. Disruption of Suv4-20h1 leads to activation of the MyoD locus and persistent stem cell activation, eventually leading to stem cell depletion and loss of skeletal muscle regeneration.
Phase I/II Trial of StemRegenin-1 Expanded Umbilical Cord Blood Hematopoietic Stem Cells Supports Testing as a Stand-Alone Graft
Bhaskar Chanda Stem Cell Clinical testing of the aryl hydrocarbon antagonist StemRegenin-1 showed robust expansion of hematopoietic stem and progenitor cells and an adequate safety profile in the setting of double UCB transplant, supporting its further testing for safety and efficacy as a stand-alone graft after myeloablative conditioning.