Linker histone regulates the myeloid versus lymphoid bifurcation of multipotent hematopoietic stem and progenitors.

ABSTRACT: Myeloid-biased differentiation of multipotent hematopoietic stem and progenitor cells (HSPCs) occurs with aging or exhaustion. The molecular mechanism(s) responsible for this fate bias remain unclear. Here, we report that linker histone regulates HSPC fate choice at the lymphoid versus myeloid bifurcation. Linker histones package nucleosomes and compact chromatin. HSPCs expressing a doxycycline (dox)-inducible H1.0 transgene favor the lymphoid fate, display strengthened nucleosome organization, and reduced chromatin accessibility at subsets of genomic regions. The genomic regions showing reduced chromatin accessibility host many known marker genes of myeloid-biased HSCs. The transcription factor Hlf is located in one of the most differentially closed regions, whose chromatin accessi

SUBMITTER: Karatepe K 

PROVIDER: S-EPMC12582276 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature