Pharmacological Reprogramming of Fibroblasts into Neural Stem Cells by Signaling-Directed Transcriptional Activation
Bhaskar Chanda Stem Cell Zhang et al. identified a cocktail of nine components that can efficiently reprogram defined mouse fibroblasts into tripotent neural stem cell-like cells and revealed that this reprogramming process involves transcriptional activation of key neurogenic regulators downstream of reprogramming signaling.
Genome Editing of Lineage Determinants in Human Pluripotent Stem Cells Reveals Mechanisms of Pancreatic Development and Diabetes
Bhaskar Chanda Stem Cell By combining genome editing and hPSC-directed differentiation, Zhu and colleagues systematically examined eight transcription factors for their roles in pancreatic development. Their study not only verified conserved gene requirements between mice and humans but also revealed a number of previously unsuspected and potentially human-specific features.
Bhaskar Chanda Stem Cell Chen et al. show that motor function in PD mice can be reversed or enhanced following transplantation of dopamine neurons differentiated from hPSCs engineered to express DREADDs. Administering CNO noninvasively and reversibly modulates neuronal graft function, highlighting the potential to exogenously control and refine therapeutic outcomes following cell transplantation.
Identification and Correction of Mechanisms Underlying Inherited Blindness in Human iPSC-Derived Optic Cups
Bhaskar Chanda Stem Cell Parfitt et al. derived human 3D optic cup organoids to model LCA, a retinal dystrophy associated with aberrant CEP290 splicing leading to cilia defects. Retinal-specific defects result from higher aberrant CEP290 splicing in photoreceptors versus other cells, and treating cups with an antisense oligonucleotide restored CEP290 protein, function, and ciliation.
Activation of Endogenous Retroviruses in ESCs Involves Disruption of SETDB1-Mediated Repression by NP95 Binding to Hemimethylated DNA
Bhaskar Chanda Stem Cell Sharif et al. show that transient derepression of proviral loci following acute depletion of Dnmt1 in ESCs is not dependent on loss of DNA methylation per se. Rather, elevated levels of hemimethylated DNA promote prolonged binding of NP95, which in turn disrupts SETDB1-dependent deposition of the repressive histone mark H3K9me3.
Bhaskar Chanda Stem Cell Mitalipov, Huang, and colleagues show that human iPSCs derived from older adults carry more mitochondrial DNA mutations than those derived from younger individuals. Defects in metabolic function caused by mtDNA mutations suggest careful screening of hiPSC clones for mutational load before clinical application.