Open AccessDifferential H4K16ac levels ensure a balance between quiescence and activation in hematopoietic stem cells
Author(s) -
Cecília Pessoa Rodrigues,
Asifa Akhtar
Publication year - 2021
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abi5987
Subject(s) - haematopoiesis , stem cell , histone acetyltransferase , microbiology and biotechnology , biology , histone , acetylation , bone marrow , hematopoietic stem cell , cancer research , leukemia , cell growth , immunology , biochemistry , gene
Hematopoietic stem cells (HSCs) are able to reconstitute the bone marrow while retaining their self-renewal property. Individual HSCs demonstrate heterogeneity in their repopulating capacities. Here, we found that the levels of the histone acetyltransferase MOF (males absent on the first) and its target modification histone H4 lysine 16 acetylation are heterogeneous among HSCs and influence their proliferation capacities. The increased proliferative capacities of MOF-depleted cells are linked to their expression of CD93. The CD93 + HSC subpopulation simultaneously shows transcriptional features of quiescent HSCs and functional features of active HSCs. CD93 + HSCs were expanded and exhibited an enhanced proliferative advantage in Mof +/- animals reminiscent of a premalignant state. Accordingly, low MOF and high CD93 levels correlate with poor survival and increased proliferation capacity in leukemia. Collectively, our study indicates H4K16ac as an important determinant for HSC heterogeneity, which is linked to the onset of monocytic disorders.