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 Srour, David A. Williams, Marie Dominique Filippi

Research output: Contribution to journalArticle

16 Citations (Scopus)

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
Pages (from-to)3557-3566
Number of pages10
JournalBlood
Volume114
Issue number17
DOIs
StatePublished - 2009

Fingerprint

Hematopoietic Stem Cells
Stem cells
Transplantation
Maintenance
rho GTP-Binding Proteins
IgA receptor
rho GTPase-activating protein
Cell- and Tissue-Based Therapy
Transducers
Cell culture
Blood Cells
Bone
Blood
Up-Regulation
Bone Marrow
Cells
Phenotype

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Xu, H., Eleswarapu, S., Geiger, H., Szczur, K., Daria, D., Zheng, Y., ... 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

Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential. / Xu, Haiming; Eleswarapu, Satyam; Geiger, Hartmut; Szczur, Kathleen; Daria, Deidre; Zheng, Yi; Settleman, Jeffrey; Srour, Edward; Williams, David A.; Filippi, Marie Dominique.

In: Blood, Vol. 114, No. 17, 2009, p. 3557-3566.

Research output: Contribution to journalArticle

Xu, H, Eleswarapu, S, Geiger, H, Szczur, K, Daria, D, Zheng, Y, Settleman, J, Srour, E, Williams, DA & Filippi, MD 2009, 'Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential', Blood, vol. 114, no. 17, pp. 3557-3566. https://doi.org/10.1182/blood-2009-02-205815
Xu, Haiming ; Eleswarapu, Satyam ; Geiger, Hartmut ; Szczur, Kathleen ; Daria, Deidre ; Zheng, Yi ; Settleman, Jeffrey ; Srour, Edward ; Williams, David A. ; Filippi, Marie Dominique. / Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential. In: Blood. 2009 ; Vol. 114, No. 17. pp. 3557-3566.
@article{a560908f9b034ea68c0e9f64d4fed2ab,
title = "Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential",
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.",
author = "Haiming Xu and Satyam Eleswarapu and Hartmut Geiger and Kathleen Szczur and Deidre Daria and Yi Zheng and Jeffrey Settleman and Edward Srour and Williams, {David A.} and Filippi, {Marie Dominique}",
year = "2009",
doi = "10.1182/blood-2009-02-205815",
language = "English",
volume = "114",
pages = "3557--3566",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "17",

}

TY - JOUR

T1 - Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential

AU - Xu, Haiming

AU - Eleswarapu, Satyam

AU - Geiger, Hartmut

AU - Szczur, Kathleen

AU - Daria, Deidre

AU - Zheng, Yi

AU - Settleman, Jeffrey

AU - Srour, Edward

AU - Williams, David A.

AU - Filippi, Marie Dominique

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=70449489421&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70449489421&partnerID=8YFLogxK

U2 - 10.1182/blood-2009-02-205815

DO - 10.1182/blood-2009-02-205815

M3 - Article

VL - 114

SP - 3557

EP - 3566

JO - Blood

JF - Blood

SN - 0006-4971

IS - 17

ER -