Differential H4K16ac levels ensure a balance between quiescence and activation in hematopoietic stem cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34362741.
- Also identified by DOI 10.1126/sciadv.abi5987 and PMC identifier 8346211.
- Licence recorded as CC BY-NC.
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Abstract
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<sup>+</sup> HSC subpopulation simultaneously shows transcriptional features of quiescent HSCs and functional features of active HSCs. CD93<sup>+</sup> HSCs were expanded and exhibited an enhanced proliferative advantage in <i>Mof</i> <sup>+/-</sup> animals reminiscent of a premalignant state. Accordingly, low <i>MOF</i> and high <i>CD93</i> 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.