Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential

Haiming Xu, Satyam Eleswarapu, Hartmut Geiger, Kathleen Szczur, Deidre Daria, Yi Zheng, Jeffrey Settleman, Edward F. Srour, David A. Williams, Marie Dominique Filippi

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Hematopoietic stem cell (HSC) engraftment is a multistep process involving HSC homing to bone marrow, self-renewal, proliferation, and differentiation to mature blood cells. Here, we show that loss of p190-B RhoGTPase activating protein, a negative regulator of Rho GTPases, results in enhanced long-term engraftment during serial transplantation. This effect is associated with maintenance of functional HSC-enriched cells. Furthermore, loss of p190-B led to marked improvement of HSC in vivo repopulation capacity during ex vivo culture without altering proliferation and multilineage differentiation of HSC and progeny. Transcriptional analysis revealed that p190-B deficiency represses the up-regulation of p16Ink4a in HSCs in primary and secondary transplantation recipients, providing a possible mechanism of p190-B-mediated HSC functions. Our study defines p190-B as a critical transducer element of HSC self-renewal activity and long-term engraftment, thus suggesting that p190-B is a target for HSC-based therapies requiring maintenance of engraftment phenotype.

Original languageEnglish (US)
Pages (from-to)3557-3566
Number of pages10
JournalBlood
Volume114
Issue number17
DOIs
StatePublished - Nov 19 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Xu, H., Eleswarapu, S., Geiger, H., Szczur, K., Daria, D., Zheng, Y., Settleman, J., Srour, E. F., Williams, D. A., & Filippi, M. D. (2009). Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential. Blood, 114(17), 3557-3566. https://doi.org/10.1182/blood-2009-02-205815