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

172 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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