Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The genome is intricately folded into chromatin compartments, topologically associating domains (TADs) and loops unique to each cell type. How this higher-order genome organization regulates cell fate transition remains elusive. Here we show how a single non-neural progenitor transcription factor, PTF1A, reorchestrates the 3D genome during fibroblast transdifferentiation into neural stem cells (NSCs). Multiomics analyses integrating Hi-C data, PTF1A and CTCF DNA-binding profiles, H3K27ac modification, and gene expression, demonstrate that PTF1A binds to subTAD boundaries subsequently associated with elevated CTCF binding and enhanced boundary insulation, and reorganizes chromatin loops, leading to gene expression changes that drive transdifferentiation into NSCs. Moreover, PTF1A activates enhancers and super-enhancers near low-insulation boundaries and modulates H3K27ac deposition, promoting cell fate transitions. Together, our data implicate an involvement of 3D genome in transcriptional and cell fate alterations, and highlight an essential role for PTF1A in gene expression control and multiscale 3D genome remodeling during cell reprogramming.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561290 | PMC |
| http://dx.doi.org/10.1038/s42003-024-07230-1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
MicroRNA-mediated regulation of proliferation, lineage differentiation, and apoptosis in neural stem cells.
RNA Biol
September 2025
Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Republic of Korea.
Neural stem cells (NSCs) are multipotent stem cells with self-renewal capacity, able to differentiate into all neural lineages of the central nervous system, including neurons, oligodendrocytes, and astrocytes; thus, their proliferation and differentiation are essential for embryonic neurodevelopment and adult brain homoeostasis. Dysregulation in these processes is implicated in neurological disorders, highlighting the need to elucidate how NSCs proliferate and differentiate to clarify the mechanisms of neurogenesis and uncover potential therapeutic targets. MicroRNAs (miRNAs) are small, post-transcriptional regulators of gene expression involved in many aspects of nervous system development and function.
View Article and Find Full Text PDFDual Role of DLK1 in GnRH Neuron Ontogeny.
Stem 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 PDFDendritic cells: understanding ontogeny, subsets, functions, and their clinical applications.
Mol Biomed
September 2025
National Key Laboratory of Immunity and Inflammation & Institute of Immunology, College of Basic Medical Sciences, Naval Medical University, Shanghai, 200433, China.
Dendritic cells (DCs) play a central role in coordinating immune responses by linking innate and adaptive immunity through their exceptional antigen-presenting capabilities. Recent studies reveal that metabolic reprogramming-especially pathways involving acetyl-coenzyme A (acetyl-CoA)-critically influences DC function in both physiological and pathological contexts. This review consolidates current knowledge on how environmental factors, tumor-derived signals, and intrinsic metabolic pathways collectively regulate DC development, subset differentiation, and functional adaptability.
View Article and Find Full Text PDFNuclear compression-mediated DNA damage drives ATR-dependent Lamin expression and mouse ESC differentiation.
Nucleic Acids Res
September 2025
Department of Biosciences & Bioengineering, IIT Bombay, Mumbai 400076, India.
Embryonic stem cells (ESCs), which are susceptible to DNA damage, depend on a robust and highly efficient DNA damage response (DDR) mechanism for their survival. However, the implications of physical force-mediated DNA damage on ESC fate remain unclear. We show that stiffness-dependent spreading of mouse ESCs (mESCs) induces DNA damage through nuclear compression, with DNA damage causing differentiation through Lamin A/C.
View Article and Find Full Text PDFSuper-Resolution Compatible DNA Labeling Technique Reveals Chromatin Mobility and Organization Changes During Differentiation.
Adv Sci (Weinh)
September 2025
Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287, Darmstadt, Germany.
Chromatin dynamics play a crucial role in cellular differentiation, yet tools for studying global chromatin mobility in living cells remain limited. Here, a novel probe is developeded for the metabolic labeling of chromatin and tracking its mobility during neural differentiation. The labeling system utilizes a newly developed silicon rhodamine-conjugated deoxycytidine triphosphate (dCTP).
View Article and Find Full Text PDF