Bhaskar Chanda Stem Cell Chen et al. showed that it is feasible to generate chimeric monkeys with contribution in all three germ layers using culture-induced naive-like state embryonic stem cells, opening up new avenues for the use of non-human primate models to study both pluripotency and human disease.
Transcriptional Mechanisms of Proneural Factors and REST in Regulating Neuronal Reprogramming of Astrocytes
Bhaskar Chanda Stem Cell Masserdotti et al. analyzed early transcriptional changes mediated by Neurog2 and Ascl1 during direct reprogramming of murine postnatal astrocytes into distinct neuronal subtypes in vitro. This led to the identification of shared downstream targets, including NeuroD4, capable of neuronal reprogramming of fibroblasts and human astrocytes, as well as mechanistic insight into how the repressor REST functions as a barrier in direct neuronal reprogramming.
Bhaskar Chanda Stem Cell Suda and colleagues show that the hematopoietic stem cell (HSC) pool integrity is coordinately controlled by p53 and its proapoptotic activator Aspp1. Aspp1 has both p53-dependent and -independent functions in regulating HSC self-renewal and DNA damage tolerance, and concomitant deletion of Aspp1 and p53 in HSCs leads to hematological malignancies.
Bhaskar Chanda Stem Cell Using mouse models of BCC, Larsimont et al. show that Sox9 is required for self-renewal of oncogene-expressing cells and BCC formation. Transcriptional profiling combined with ChIP sequencing uncovered a cancer-specific gene network regulated by Sox9 that promotes stemness, represses differentiation, and induces ECM and cytoskeleton remodeling required for tumor invasion.
Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions
Bhaskar Chanda Stem Cell Pietras et al. show that HSCs produce functionally distinct lineage-biased MPPs that work together to adapt blood production to hematopoietic demands. Two rare subsets of myeloid-biased MPPs are important for maintaining blood homeostasis at steady state and serve as a potent source of myeloid amplification in regenerative conditions.
Epigenetic Regulation of Phosphodiesterases 2A and 3A Underlies Compromised β-Adrenergic Signaling in an iPSC Model of Dilated Cardiomyopathy
Bhaskar Chanda Stem Cell In this paper, Wu et al. profiled the β-adrenergic signaling properties in human iPSC-CMs and demonstrated novel epigenetic mechanisms that underlie the compromised β-adrenergic signaling in DCM, a common cause of heart failure and cardiac transplantation. These results enhance our understanding of DCM pathogenesis and may uncover new therapeutic targets.