Bhaskar Chanda Stem Cell The growth and structural formation of the human cortex can be modeled in vitro using cerebral organoids. In this article, Li, Muffat, and colleagues show that enhancing the PTEN-AKT signaling pathway leads to the generation of human cerebral organoids that are expanded in size and display surface folding.
Bhaskar Chanda Stem Cell Bcl11b interacts with cell-cycle regulators to induce a quiescent state. Cai et al. describe a quiescent mammary stem cell population labeled by Bcl11b and located at the luminal-basal interface that supports mammary gland regeneration. Bcl11b sustains this population by inducing cell-cycle regulators that promote the dormant state.
Bhaskar Chanda Stem Cell Cheng and colleagues using Raman spectroscopic imaging find that ovarian cancer stem cells contain unusually high levels of unsaturated lipids and show evidence that this metabolic difference could be used as a marker for these cells and as a new target for CSC-specific therapy.
Bhaskar Chanda Stem Cell Li and colleagues reported that tissue damage enables in vivo reprogramming in skeletal muscle, which can arise from muscle stem cells. They also show that damage-induced cellular senescence promotes cellular plasticity through release of secreted proteins, including IL-6. Their findings could have implications for developing therapeutic lineage reprogramming strategies.
Analysis of Transcriptional Variability in a Large Human iPSC Library Reveals Genetic and Non-genetic Determinants of Heterogeneity
Bhaskar Chanda Stem Cell Using large-scale analyses of over 300 iPSC lines, Chang, Quertermous, Lemischka, and colleagues of the NHLBI NextGen consortium examine sources of gene expression variation between lines and illustrate how this approach can identify genetic and non-genetic drivers relevant to line variation with implications for iPSC characterization and disease modeling.
Patient-Specific iPSC-Derived Endothelial Cells Uncover Pathways that Protect against Pulmonary Hypertension in BMPR2 Mutation Carriers
Bhaskar Chanda Stem Cell As part of the NHLBI NextGen consortium, Gu et al. report protective mechanisms of potential therapeutic significance in unaffected BMPR2 mutation carrier (UMC) iPSC-derived endothelial cells (iPSC-ECs) versus iPSC-ECs from family members with pulmonary arterial hypertension (FPAH). Their findings about changes in specific regulators could inform future therapy development.
Bhaskar Chanda Stem Cell Liau et al. find that glioblastoma stem cells (GSCs) reversibly transition to a slow-cycling, persister-like state following RTK inhibitor treatment. The persister state is marked by redistribution of repressive chromatin, upregulation of neurodevelopmental programs, and dependency on KDM6. Thus, cancer cells may hijack chromatin reorganization for proliferation, adaptation, and tolerance.
Bhaskar Chanda Stem Cell Rougeulle and colleagues show that, in human pre-implantation embryos and naive human embryonic stem cells, the lncRNAs XIST and XACT accumulate together on active X chromosomes. Functional data suggest that XACT restrains XIST activity before the initiation of X inactivation takes place.
Bhaskar Chanda Stem Cell Plath and colleagues study the epigenetic state of the X chromosomes in naive female hPSCs and discover that it closely, but not perfectly, resembles the X chromosome pattern of pre-implantation blastocysts. The naive state enables de novo X inactivation upon differentiation and thus can provide a model for studying X chromosome regulation in human cells.
A Multi-step Transcriptional and Chromatin State Cascade Underlies Motor Neuron Programming from Embryonic Stem Cells
Bhaskar Chanda Stem Cell Mazzoni and colleagues show that transcription factor-directed programming of ESCs to motor neurons involves two distinct regulatory modules that converge when programming TFs are relocated by the activity of factors induced in the earlier stage of the process.