Cytokines regulate postnatal hematopoietic stem cell expansion: opposing roles of thrombopoietin and LNK (original) (raw)

  1. Natalija Buza-Vidas1,3,
  2. Jennifer Antonchuk1,3,
  3. Hong Qian1,
  4. Robert Månsson1,
  5. Sidinh Luc1,
  6. Sasan Zandi1,
  7. Kristina Anderson1,
  8. Satoshi Takaki2,
  9. Jens M. Nygren1,
  10. Christina T. Jensen1, and
  11. Sten Eirik W. Jacobsen1,4
  12. 1 Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, 22184 Lund, Sweden;
  13. 2 Department of Community Health and Medicine, Research Institute, International Medical Center of Japan, 162-8655 Shinjuku-ku, Tokyo, Japan
  14. ↵3 These authors contributed equally to the work.

Abstract

The role of cytokines as regulators of hematopoietic stem cell (HSC) expansion remains elusive. Herein, we identify thrombopoietin (THPO) and the cytokine signaling inhibitor LNK, as opposing physiological regulators of HSC expansion. Lnk−/− HSCs continue to expand postnatally, up to 24-fold above normal by 6 mo of age. Within the stem cell compartment, this expansion is highly selective for self-renewing long-term HSCs (LT-HSCs), which show enhanced THPO responsiveness. Lnk−/− HSC expansion is dependent on THPO, and 12-wk-old Lnk−/−Thpo−/− mice have 65-fold fewer LT-HSCs than Lnk−/− mice. Expansions of multiple myeloid, but not lymphoid, progenitors in Lnk−/− mice also proved THPO-dependent.

Footnotes