P190-B RhoGAP and intracellular cytokine signals balance hematopoietic stem and progenitor cell self-renewal and differentiation

Ashwini Hinge, Juying Xu, Jose Javier, Eucabeth Mose, Sachin Kumar, Reuben Kapur, Edward Srour, Punam Malik, Bruce J. Aronow, Marie Dominique Filippi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The mechanisms regulating hematopoietic stem and progenitor cell (HSPC) fate choices remain ill-defined. Here, we show that a signalling network of p190-B RhoGAP-ROS-TGF-β-p38 MAPK balances HSPC self-renewal and differentiation. Upon transplantation, HSPCs express high amounts of bioactive TGF-β1 protein, which is associated with high levels of p38 MAPK activity and loss of HSC self-renewal in vivo. Elevated levels of bioactive TGF-β1 are associated with asymmetric fate choice in vitro in single HSPCs via p38MAPK activity and this is correlated with the asymmetric distribution of activated p38MAPK. In contrast, loss of p190-B, a RhoGTPase inhibitor, normalizes TGF-β levels and p38MAPK activity in HSPCs and is correlated with increased HSC self-renewal in vivo. Loss of p190-B also promotes symmetric retention of multi-lineage capacity in single HSPC myeloid cell cultures, further suggesting a link between p190-B-RhoGAP and non-canonical TGF-β signalling in HSPC differentiation. Thus, intracellular cytokine signalling may serve as 'fate determinants' used by HSPCs to modulate their activity.

Original languageEnglish (US)
Article number14382
JournalNature Communications
Volume8
DOIs
StatePublished - Feb 8 2017

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stem cells
Hematopoietic Stem Cells
stems
p38 Mitogen-Activated Protein Kinases
Cytokines
activity (biology)
cells
Cell culture
transplantation
determinants
inhibitors
proteins
Cell Self Renewal
Proteins
Myeloid Cells
Cell Differentiation
Cell Culture Techniques
Transplantation

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

P190-B RhoGAP and intracellular cytokine signals balance hematopoietic stem and progenitor cell self-renewal and differentiation. / Hinge, Ashwini; Xu, Juying; Javier, Jose; Mose, Eucabeth; Kumar, Sachin; Kapur, Reuben; Srour, Edward; Malik, Punam; Aronow, Bruce J.; Filippi, Marie Dominique.

In: Nature Communications, Vol. 8, 14382, 08.02.2017.

Research output: Contribution to journalArticle

Hinge, Ashwini ; Xu, Juying ; Javier, Jose ; Mose, Eucabeth ; Kumar, Sachin ; Kapur, Reuben ; Srour, Edward ; Malik, Punam ; Aronow, Bruce J. ; Filippi, Marie Dominique. / P190-B RhoGAP and intracellular cytokine signals balance hematopoietic stem and progenitor cell self-renewal and differentiation. In: Nature Communications. 2017 ; Vol. 8.
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