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Cold Spring Harbor Laboratory Press, Genes & Development, 15(20), p. 2018-2023, 2006

DOI: 10.1101/gad.385606

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Cytokines regulate postnatal hematopoietic stem cell expansion : Opposing roles of thrombopoietin and LNK

Journal article published in 2006 by Hong Qian, Robert Månsson ORCID, Sidinh Luc, Sasan Zandi, Jennifer Antonchuk, Natalija Buza-Vidas, Satoshi Takaki, Jens Martin Nygren, Christina T. Jensen, Kristina Anderson, Sten Eirik W. Jacobsen
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.