Ground State Conditions Induce Rapid Reorganization of Core Pluripotency Factor Binding before Global Epigenetic Reprogramming
Bhaskar Chanda Stem Cell Meissner and colleagues provide a comprehensive characterization of the early OCT4, SOX2, and NANOG binding dynamics during the transition from serum/LIF to 2i. The target rewiring predominantly affects distal regulatory elements with a plausible link to the upstream signaling pathways. Notably, these events appear before any major epigenetic reprogramming events, which occur only later in the transition.
Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury
Bhaskar Chanda Stem Cell Llorens-Bobadilla et al. perform single-cell RNA sequencing of acutely isolated neural stem cells (NSCs) from the adult SVZ, identifying lineage-primed NSCs residing along a continuum of co-existing states between dormancy and activation. NSCs in different states possess unique molecular features and exhibit differential responses to acute ischemic brain injury.
Functional Correction of Large Factor VIII Gene Chromosomal Inversions in Hemophilia A Patient-Derived iPSCs Using CRISPR-Cas9
Bhaskar Chanda Stem Cell Park et al. used CRISPR-Cas9 in patient iPSCs to correct two large inversions that are the most common underlying mutations for severe hemophilia, and they show that the correction is functional by rescuing lethality in hemophiliac mice using iPSC-derived endothelial cells.
Bhaskar Chanda Stem Cell Reya and colleagues identify Tetraspanin 3 as a key signal required for AML. Tspan3 deletion leads to improved survival in mouse models of AML and reduced cancer growth in xenografts. Tspan3 loss impairs migration of leukemic cells to SDF suggesting that it may influence oncogenesis by controlling a normal chemokine response.
Bhaskar Chanda Stem Cell Saitou and colleagues report induction of human primordial germ cell-like cells (hPGCLCs) from pluripotent stem cells. hPGCLC and mouse PGC specification rely on similar signaling pathways but utilize distinct transcriptional programs, highlighting differences in PGC induction and demonstrating the utility of hPGCLCs for studying human germ cell development in vitro.
CRISPR-Cas9-Mediated Genetic Screening in Mice with Haploid Embryonic Stem Cells Carrying a Guide RNA Library
Bhaskar Chanda Stem Cell Li and colleagues show that the combined application of altered expression of two imprinted genes and CRISPR-Cas9-based genome editing allows the efficient and stable generation of gene-modified semi-cloned mice from androgenetic haploid embryonic stem cells. This approach has potential for mutagenesis and screening.
Runx1 Deficiency Decreases Ribosome Biogenesis and Confers Stress Resistance to Hematopoietic Stem and Progenitor Cells
Bhaskar Chanda Stem Cell Loss-of-function RUNX1 mutations are common in myelodysplastic syndrome and leukemia and can be early events. Cai et al. demonstrate that Runx1 loss decreases ribosome biogenesis and translation in hematopoietic stem and progenitor cells and confers resistance to endogenous and genotoxic stress.
Bhaskar Chanda Stem Cell By combining CRISPR/Cas9-mediated genome editing with the Flp/FRT and Cre/LoxP system, Chen et al. developed an efficient two-step strategy to generate inducible gene knockout hPSC lines with predictable gene mutations upon tamoxifen treatment at any stages of differentiation. The iKO hPSC lines will enable the elucidation of gene functions throughout differentiation.