Rac and Cdc42 GTPases control hematopoietic stem cell shape, adhesion, migration, and mobilization

F. C. Yang, S. J. Atkinson, Y. Gu, J. B. Borneo, A. W. Roberts, Y. Zheng, J. Pennington, D. A. Williams

Research output: Contribution to journalArticlepeer-review

151 Scopus citations

Abstract

Critical to homeostasis of blood cell production by hematopoietic stem/progenitor (HSC/P) cells is the regulation of HSC/P retention within the bone marrow microenvironment and migration between the bone marrow and the blood. Key extracellular regulatory elements for this process have been defined (cell-cell adhesion, growth factors, chemokines), but the mechanism by which HSC/P cells reconcile multiple external signals has not been elucidated. Rac and related small GTPases are candidates for this role and were studied in HSC/P deficient in Rac2, a hematopoietic cell-specific family member. Rac2 appears to be critical for HSC/P adhesion both in vitro and in vivo, whereas a compensatory increase in Cdc42 activation regulates HSC/P migration. This genetic analysis provides physiological evidence of cross-talk between GTPase proteins and suggests that a balance of these two GTPases controls HSC/P adhesion and mobilization in vivo.

Original languageEnglish (US)
Pages (from-to)5614-5618
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number10
DOIs
StatePublished - May 8 2001
Externally publishedYes

ASJC Scopus subject areas

  • General

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