Lnk negatively regulates self-renewal of hematopoietic stem cells by modifying thrombopoietin-mediated signal transduction.

ABSTRACT: One of the central tasks of stem cell biology is to understand the molecular mechanisms that control self-renewal in stem cells. Several cytokines are implicated as crucial regulators of hematopoietic stem cells (HSCs), but little is known about intracellular signaling for HSC self-renewal. To address this issue, we attempted to clarify how self-renewal potential is enhanced in HSCs without the adaptor molecule Lnk, as in Lnk-deficient mice HSCs are expanded in number >10-fold because of their increased self-renewal potential. We show that Lnk negatively regulates self-renewal of HSCs by modifying thrombopoietin (TPO)-mediated signal transduction. Single-cell cultures showed that Lnk-deficient HSCs are hypersensitive to TPO. Competitive repopulation revealed that long-term repopulating act

SUBMITTER: Seita J 

PROVIDER: S-EPMC1892983 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature