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Cited by 407Hematopoietic Stem Cell TransplantationChemokine receptors and signalingMesenchymal stem cell research

CXCR4 is required for the quiescence of primitive hematopoietic cells

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Nie, Yuchun, Han, Yoon-Chi, Zou, Yong-Rui·2008·The Journal of Experimental Medicine
DOI 10.1084/jem.20072513PMC PMC2292218
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Abstract

The quiescence of hematopoietic stem cells (HSCs) is critical for preserving a lifelong steady pool of HSCs to sustain the highly regenerative hematopoietic system. It is thought that specialized niches in which HSCs reside control the balance between HSC quiescence and self-renewal, yet little is known about the extrinsic signals provided by the niche and how these niche signals regulate such a balance. We report that CXCL12 produced by bone marrow (BM) stromal cells is not only the major chemoattractant for HSCs but also a regulatory factor that controls the quiescence of primitive hematopoietic cells. Addition of CXCL12 into the culture inhibits entry of primitive hematopoietic cells into the cell cycle, and inactivation of its receptor CXCR4 in HSCs causes excessive HSC proliferation. Notably, the hyperproliferative Cxcr4−/− HSCs are able to maintain a stable stem cell compartment and sustain hematopoiesis. Thus, we propose that CXCR4/CXCL12 signaling is essential to confine HSCs in the proper niche and controls their proliferation.

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  • CD9 and VWF are closely associated with MkP differentiation.

    “In the MkPs, we identified a downregulation of CD9 and VWF , closely associated with MkP differentiation 46-49 , upon IFNa treatment ( Supplementary Fig. 4b ) which is consistent with the decrease in the proportion of MkP observed after IFNa treatment.”

    From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [47]

    The Results and Discussion passages address CXCR4-dependent hematopoietic stem-cell quiescence and differentiation, not MkP differentiation. Searches for CD9, VWF, megakaryocyte progenitors, and related terms found no passage connecting either marker to MkP differentiation. Page numbers were not available in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • In MkPs, CD9 and VWF were downregulated upon IFNa treatment.

    “In the MkPs, we identified a downregulation of CD9 and VWF , closely associated with MkP differentiation 46-49 , upon IFNa treatment ( Supplementary Fig. 4b ) which is consistent with the decrease in the proportion of MkP observed after IFNa treatment.”

    From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [47]

    The citation is attached to the statement that CD9 and VWF are associated with MkP differentiation; the IFNa-treatment result is presented as the citing authors’ own finding. The cited paper’s Results and Discussion passage on cell-cycle regulation concerns CXCR4, CXCL12, and p57kip2 in primitive hematopoietic cells. Searches for CD9, VWF, MkPs, and IFNa found no passage addressing the cited association or the treatment result. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 26

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Sorted by citations

Authors
Nie, Y., Han, Y.-C., & Zou, Y.-R.
Affiliations
Columbia University (US)
ORCID
Zou, Yong-Rui
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2008-03-31
Volume
205
Issue
4
Pages
777-783
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20072513
PMC
PMC2292218
OpenAlex
W2165225182
Cited by
407
References
0
Citations by year
2026: 10 · 2025: 11 · 2024: 19 · 2023: 16 · 2022: 14 · 2021: 24 · 2020: 33 · 2019: 12 · 2018: 20 · 2017: 25 · 2016: 25 · 2015: 24 · 2014: 25 · 2013: 32 · 2012: 34
FWCI
17.96
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
CXCR4, CXCL12, hematopoietic stem cells, HSC quiescence, HSC proliferation, mesenchymal stem cells, hematopoietic niche, cell cycle entry, stem cell self-renewal, hematopoiesis
MeSH terms
Animals, Bone Marrow Cells, Cell Cycle, Hematopoiesis, Hematopoietic Stem Cells, Hematopoietic System, Signal Transduction, Receptors, CXCR4, Multipotent Stem Cells, Cell Proliferation, Mice, Chemokine CXCL12

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