Cytokines regulate postnatal hematopoietic stem cell expansion: Opposing roles of thrombopoietin and LNK
2006 (English)In: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 20, no 15, 2018-2023 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Woodbury, NY, USA: Cold Spring Harbor Laboratory Press (CSHL), 2006. Vol. 20, no 15, 2018-2023 p.
Hematopoiesis, LNK, Self-renewal, Stem cells, Thrombopoietin
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:hh:diva-15175DOI: 10.1101/gad.385606ISI: 000239504500007PubMedID: 16882979ScopusID: 2-s2.0-33746591727OAI: oai:DiVA.org:hh-15175DiVA: diva2:419613