Rac2-deficient hematopoietic stem cells show defective interaction with the hematopoietic microenvironment and long-term engraftment failure

Michael Jansen, Feng-Chun Yang, José A. Cancelas, Jeff R. Bailey, David A. Williams

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The hematopoietic-specific Rho GTPase, Rac2, regulates a variety of cellular functions including cell shape changes, motility, integrin-dependent adhesion, and apoptosis. In the study reported here, we demonstrate that wild-type (WT) hematopoietic stem cells/progenitors (HSC/P) preferentially engraft in nonablated Rac2-/-bone marrow. In addition, primitive Rac2-/- HSC/P transplanted into lethally irradiated WT recipients showed a significant competitive defect compared with WT cells. These defects appeared to be related to HSC/P-intrinsic defective microenvironment interactions, since Rac2-/- cells showed less adhesion to the femur bone marrow density 1 (FBMD-1) stromal cell line, a lower frequency of cobblestone area-forming cells, and lower performance in long-term marrow cultures in vitro when compared with WT cells. In contrast, primitive Rac2 -/- hematopoietic cells exhibited normal progenitor colony formation in semisolid medium in vitro and normal proliferation in the steady state in vivo when compared with WT cells. Taken together, these data suggest that Rac2-/-stem/progenitor cells exhibit abnormal interaction with the hematopoietic microenvironment, which leads to defective long-term engraftment.

Original languageEnglish (US)
Pages (from-to)335-346
Number of pages12
JournalStem Cells
Volume23
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

Fingerprint

Hematopoietic Stem Cells
Bone Marrow
Stem Cells
rho GTP-Binding Proteins
Cell Shape
Stromal Cells
Integrins
Bone Density
Femur
Apoptosis
Cell Line

Keywords

  • Engraftment
  • Homing
  • RAC
  • RhoGTPase
  • Stem Cells

ASJC Scopus subject areas

  • Cell Biology

Cite this

Rac2-deficient hematopoietic stem cells show defective interaction with the hematopoietic microenvironment and long-term engraftment failure. / Jansen, Michael; Yang, Feng-Chun; Cancelas, José A.; Bailey, Jeff R.; Williams, David A.

In: Stem Cells, Vol. 23, No. 3, 03.2005, p. 335-346.

Research output: Contribution to journalArticle

Jansen, Michael ; Yang, Feng-Chun ; Cancelas, José A. ; Bailey, Jeff R. ; Williams, David A. / Rac2-deficient hematopoietic stem cells show defective interaction with the hematopoietic microenvironment and long-term engraftment failure. In: Stem Cells. 2005 ; Vol. 23, No. 3. pp. 335-346.
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