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Human neural development begins at embryonic day 19 and marks the beginning of organogenesis. Neural stem cells in the neural tube undergo profound functional, morphological, and metabolic changes during neural specification, coordinated by a combination of exogenous and endogenous cues. The temporal cell signaling activities that mediate this process, during development and in the postnatal brain, are incompletely understood. We have applied gene expression studies and transcription factor-activated reporter lentiviruses during in vitro neural specification of human pluripotent stem cells. We show that nuclear factor κB orchestrates a multi-faceted metabolic program necessary for the maturation of neural progenitor cells during neurogenesis.
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http://dx.doi.org/10.1016/j.stemcr.2018.03.015 | DOI Listing |
Drug Des Devel Ther
September 2025
Department of Neurosurgery, Peking University People's Hospital, Beijing, People's Republic of China.
Introduction: Parkinson's disease (PD) is a neurodegenerative disorder lacking therapies to replace lost dopaminergic neurons. Neural stem cell (NSC) transplantation faces survival and differentiation challenges. This study investigated feasibility and efficacy of paeoniflorin (PF) combined with NSC transplantation for PD treatment.
View Article and Find Full Text PDFEMBO Mol Med
September 2025
Institute for Regenerative Medicine, Medical Innovation Center and State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, National Stem Cell Translational Resource Center & Ministry of Education Stem Cell Resource Center, Frontier Science Center for Stem Cell Research, School of Li
Primary microcephaly, a rare congenital condition characterized by reduced brain size, occurs due to impaired neurogenesis during brain development. Through whole-exome sequencing, we identified compound heterozygous loss-of-function mutations in CENTRIN 3 (CETN3) in a 5-year-old patient with primary microcephaly. As CETN3 has not been previously linked to microcephaly, we investigated its potential function in neurodevelopment in human pluripotent stem cell-derived cerebral organoids.
View Article and Find Full Text PDFOpen Biol
September 2025
National Brain Research Centre, Manesar, Haryana, India.
E3 ubiquitin ligases regulate the cellular proteome proteasome-dependent protein degradation; however, there exist limited studies outlining their non-canonical functions. RNA-binding ubiquitin ligases (RBULs) represent a subset of E3 ligases that harbour RNA-binding domains, making them uniquely positioned to function as both RNA-binding proteins and E3 ligases. Our initial microarray screen for E3 ligases from mouse cortical neural progenitor cells identified MEX3B, a known RNA-binding ubiquitin ligase, to be differentially expressed.
View Article and Find Full Text PDFStem Cell Rev Rep
September 2025
Stem Cells and Metabolism Research Program (STEMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.
Mutations in Delta Like Non-Canonical Notch Ligand 1 (DLK1), a paternally expressed imprinted gene, underlie central precocious puberty (CPP), yet the mechanism remains unclear. To test the hypothesis that DLK1 plays a role in gonadotropin releasing hormone (GnRH) neuron ontogeny, 75 base pairs were deleted in both alleles of DLK1 exon 3 with CRISPR-Cas9 in human pluripotent stem cells (hPSCs). This line, exhibiting More than 80% loss of DLK1 protein, was differentiated into GnRH neurons by dual SMAD inhibition (dSMADi), FGF8 treatment and Notch inhibition, as previously described, however, it did not exhibit accelerated GNRH1 expression.
View Article and Find Full Text PDFJ Vis Exp
August 2025
Department of Oncology, Division of Pediatric Oncology and Institute for Cell Engineering, The Johns Hopkins University School of Medicine;
Human cord blood (CB) myeloid progenitor reprogramming to a high-fidelity human induced pluripotent stem cell (hiPSC) state can be achieved using non-integrating episomal vectors and stromal signals. These conventional, primed CB-hiPSC lines can subsequently be chemically reverted with high efficiencies to a blastomere-like Tankyrase/PARP Inhibitor-Regulated Naive Stem Cell (TIRN-SC) state with functional totipotency. PARP-regulated TIRN-SCs are human stem cells with high epigenetic plasticity, stable epigenomic imprints, and have greater differentiation potency than conventional, lineage-primed hiPSCs.
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