Ptpn21 Controls Hematopoietic Stem Cell Homeostasis and Biomechanics

Cell Stem Cell. 2019 Apr 4;24(4):608-620.e6. doi: 10.1016/j.stem.2019.02.009. Epub 2019 Mar 14.


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 remodeling, contributed to cortical instability, and decreased cell rigidity. Collectively, these findings show that Ptpn21 maintains cellular mechanics, which is correlated with its important functions in HSC niche retention and preservation of hematopoietic regeneration capacity.

Keywords: Ptpn21; biomechanics; cytoskeleton; hematopoietic stem cell; niche; protein tyrosine phosphatase; septin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Homeostasis*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphorylation
  • Protein Tyrosine Phosphatases, Non-Receptor / deficiency
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism*
  • Septins / metabolism*
  • Stem Cell Niche


  • Protein Tyrosine Phosphatases, Non-Receptor
  • Ptpn21 protein, mouse
  • Sept1 protein, mouse
  • Septins