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The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
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The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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Neural stem cell quiescence is actively maintained by the epigenome.

Anna Malkowska1, Jan Ander2, Andrea H Brand1

  • 1Department of Cell Biology and Regenerative Medicine Institute, New York University Grossman School of Medicine, New York, NY, USA; Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.

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|December 19, 2025
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Summary

Neural stem cells (NSCs) maintain nervous system homeostasis. During quiescence, their chromatin opens, but cell cycle genes are repressed, while cell communication genes are activated.

Keywords:
CP: molecular biologyCP: stem cell researchTargeted DamIDchromatinhistone modificationquiescencestem cell

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Area of Science:

  • Neuroscience
  • Stem Cell Biology
  • Epigenetics

Background:

  • Neural stem cells (NSCs) maintain nervous system homeostasis through quiescence, a reversible cell-cycle arrest.
  • NSC reactivation is crucial for physiological responses and involves epigenomic regulation.
  • Understanding epigenomic changes during NSC quiescence and reactivation is key to neural repair.

Purpose of the Study:

  • To map epigenomic changes in neural stem cell (NSC) chromatin during quiescence and reactivation in Drosophila.
  • To investigate the relationship between chromatin accessibility, gene expression, and cell-cycle status in quiescent and reactivating NSCs.

Main Methods:

  • In vivo epigenomic profiling in Drosophila melanogaster.
  • Chromatin accessibility assays (e.g., ATAC-seq).
  • Histone modification analysis (e.g., ChIP-seq for H3K36me3, H1, SWI/SNF components).
  • Gene expression analysis (e.g., RNA-seq).

Main Results:

  • Contrary to expectations, chromatin accessibility globally increases in quiescent NSCs.
  • Genes critical for cell-cycle progression are repressed despite being in accessible euchromatin.
  • Genes involved in cell-cell communication are upregulated due to histone H1 eviction and SWI/SNF complex enrichment.
  • Chromatin opening is a dynamic, quiescence-specific event that reverses upon NSC reactivation.

Conclusions:

  • Quiescent NSCs exhibit a unique epigenomic state characterized by increased chromatin accessibility without widespread transcriptional activation.
  • Chromatin remodeling plays a critical role in regulating gene expression programs during NSC quiescence and reactivation.
  • These findings provide novel insights into the regulation of neural stem cell fate and potential therapeutic targets for neurological disorders.