Ptpn21 Controls Hematopoietic Stem Cell Homeostasis and Biomechanics.

ABSTRACT: Hematopoietic stem cell (HSC) quiescence is a tightly regulated process crucial for hematopoietic regeneration, which requires a healthy and supportive microenvironmental niche within the bone marrow (BM). Here, we show that deletion of Ptpn21, a protein tyrosine phosphatase highly expressed in HSCs, induces stem cell egress from the niche due to impaired retention within the BM. Ptpn21^-/- HSCs exhibit enhanced mobility, decreased quiescence, increased apoptosis, and defective reconstitution capacity. Ptpn21 deletion also decreased HSC stiffness and increased physical deformability, in part by dephosphorylating Spetin1 (Tyr²⁴⁶), a poorly described component of the cytoskeleton. Elevated phosphorylation of Spetin1 in Ptpn21^-/- cells impaired cytoskeletal rem

SUBMITTER: Ni F 

PROVIDER: S-EPMC6450721 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature