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Mettl3-dependent m6A targets in adult murine hematopoietic stem cells

ABSTRACT: Hematopoietic stem cells (HSCs) maintain balanced self-renewal and differentiation according to physiological demands, but how different facets of these functions are precisely regulated is not fully understood. N6-methyladenosine (m6A) mRNA methylation has emerged as an important mode of epitranscriptional gene expression regulation affecting many biological processes. We show that deleting the m6A methyltransferase, Mettl3, from the adult hematopoietic system led to an accumulation of HSCs in the bone marrow and marked reduction of HSC reconstitution potential due to a blockage of HSC differentiation. Interestingly, deleting Mettl3 from myeloid cells using Lysm-cre did not have any discernable impact on myeloid cell number or function. m6A sequencing on purified HSCs revealed 2,073 genes with significant m6A modification. In particular, Myc, a key regulator of HSC differentiation, was identified as a direct target of m6A in HSCs. Mettl3-deficient HSCs failed to up-regulate Myc expression upon stimulation to differentiate and enforced expression of Myc rescued differentiation defects of Mettl3-deficient HSCs. Our results thus revealed a key role of m6A in governing HSC differentiation by regulating Myc expression. This data includes m6A sequencing data on HSCs from wild-type or Mettl3-deficient mice, revealing the Mettl3-depedent m6A targets in HSCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE123525 | GEO | 2019/03/31

REPOSITORIES: GEO

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