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

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16 Scopus citations


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
Issue number17
StatePublished - Nov 19 2009


ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

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