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Cxcl10 and Cxcr3 regulate self-renewal and differentiation of hematopoietic stem cells

Fangshu Liu1, Xiaofan Sun1, Suqi Deng1

  • 1Department of Hematology, The First Affiliated Hospital of Jinan University, 613W Huangpu Rd, Guangzhou, Guangdong, 510632, China.

Stem Cell Research & Therapy
|August 7, 2024
PubMed

Insights

The chemokine CXCL10 and its receptor CXCR3 are crucial for regulating hematopoietic stem cell (HSC) self-renewal and differentiation. Their absence impairs HSC function, impacting blood cell production.

Area of Science:

  • Hematology
  • Immunology
  • Stem Cell Biology

Background:

  • Hematopoietic stem cell (HSC) function is governed by intrinsic signaling and microenvironmental cues.
  • Chemokines and their ligands are known regulators of HSCs, but their precise roles remain incompletely understood.

Purpose of the Study:

  • To investigate the specific roles of the chemokine CXCL10 and its receptor CXCR3 in regulating HSC self-renewal and differentiation.
  • To elucidate the impact of Cxcl10 and Cxcr3 deficiency on HSC function and bone marrow cellularity.

Main Methods:

  • Generation of Cxcr3 and Cxcl10 knockout mouse models (Cxcr3-/- and Cxcl10-/-).
  • Assessment of long-term HSC (LT-HSC) cell cycle distribution using flow cytometry.
  • Serial transplantation assays to evaluate HSC self-renewal capacity.
  • Bone marrow microenvironment analysis through transplantation of donor cells into knockout recipients.

Main Results:

  • Cxcl10 and Cxcr3 deficiency resulted in reduced bone marrow cellularity and an increased proportion of LT-HSCs.
  • Cxcl10-/- stem/progenitor cells exhibited diminished self-renewal capacity and a bias towards B lymphocyte differentiation.
  • Cxcr3-deficient HSCs showed impaired reconstitution in secondary transplantation, though lineage bias was not significant.
  • Absence of Cxcl10 or Cxcr3 within the bone marrow microenvironment did not impact HSC function.

Conclusions:

  • CXCL10 and CXCR3 play significant roles in regulating HSC self-renewal and differentiation.
  • These findings enhance the understanding of chemokine-mediated regulation of HSC function.
Abstract

Keywords:
C-X-C motif chemokine ligand 10C-X-C motif chemokine receptor 3Competitive bone marrow transplantationHematopoietic stem cellsSelf-renewal

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