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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.

Original publication

DOI

10.1101/gad.385606

Type

Journal article

Journal

Genes Dev

Publication Date

01/08/2006

Volume

20

Pages

2018 - 2023

Keywords

Animals, Colony-Forming Units Assay, Cytokines, Female, Gene Expression Regulation, Developmental, Hematopoiesis, Hematopoietic Stem Cells, Intracellular Signaling Peptides and Proteins, Lymphocytes, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Myeloid Cells, Proteins, Signal Transduction, Stem Cells, Thrombopoietin