MiR-143/145 differentially regulate hematopoietic stem and progenitor activity through suppression of canonical TGFβ signaling.

ABSTRACT: Expression of miR-143 and miR-145 is reduced in hematopoietic stem/progenitor cells (HSPCs) of myelodysplastic syndrome patients with a deletion in the long arm of chromosome 5. Here we show that mice lacking miR-143/145 have impaired HSPC activity with depletion of functional hematopoietic stem cells (HSCs), but activation of progenitor cells (HPCs). We identify components of the transforming growth factor β (TGFβ) pathway as key targets of miR-143/145. Enforced expression of the TGFβ adaptor protein and miR-145 target, Disabled-2 (DAB2), recapitulates the HSC defect seen in miR-143/145^-/- mice. Despite reduced HSC activity, older miR-143/145^-/- and DAB2-expressing mice show elevated leukocyte counts associated with increased HPC activity. A subset of mice develop a

SUBMITTER: Lam J 

PROVIDER: S-EPMC6010451 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature