Evidence map›Paper›PMID 32159901›Full record

ArticleStem cells (Dayton, Ohio)2020

CXCR4 expression in the bone marrow microenvironment is required for hematopoietic stem and progenitor cell maintenance and early hematopoietic regeneration after myeloablation.

Pratibha Singh, Khalid S Mohammad, Louis M Pelus

Open access · greenAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
  2. Review
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  5. Searching for a HIV-1 Cure.Theranostics · 2026
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  7. Microvesicles secreted by CoClAnnals of hematology · 2025
    Article
  8. Article
  9. Review
  10. Article
  11. Review
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  15. Leukemic Stem Cells and Hematological Malignancies.International journal of molecular sciences · 2024
    Review
  16. Article
  17. Review
  18. Article
  19. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Pratibha SinghDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.ORCID 0000-0002-6571-1271
Khalid S MohammadDepartment of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Louis M PelusDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Indiana University School of Medicine

Funding

Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI Jun Wan · 1999 to 2026
$59.3M
Role of PGE2 and other eicosanoids in hematopoietic stem cell functionR01HL096305 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI PELUS, LOUIS M · 2010 to 2018
$3.5M
Inhibition of PGE2 for mobilization of autologous peripheral blood stem cellsR01CA182947 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI FARAG, SHERIF S, PELUS, LOUIS M · 2014 to 2018
$1.6M
A megakaryocyte/PGE2/osteoblast triad in the normal and aged nicheR01AG046246 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI KACENA, MELISSA A, PELUS, LOUIS M · 2013 to 2017
$1.1M
Age-Related Differences in Response to Radiation and Medical CountermeasuresUH3AI128894 · NIAID · INDIANA UNIVERSITY INDIANAPOLIS · PI ORSCHELL, CHRISTIE M, PELUS, LOUIS M · 2018 to 2020
$450k
Age-Related Differences in Response to Radiation and Medical CountermeasuresUH2AI128894 · NIAID · INDIANA UNIVERSITY INDIANAPOLIS · PI ORSCHELL, CHRISTIE M, PELUS, LOUIS M · 2016 to 2017
$150k
NCI NIH HHS P30 CA082709NCI NIH HHS R01 CA182947NHLBI NIH HHS R01 HL096305NIAID NIH HHS UH2 AI128894NIAID NIH HHS UH3 AI128894NIA NIH HHS R01 AG046246
6 · The paper itself

Abstract

The bone marrow (BM) microenvironment/niche plays a key role in regulating hematopoietic stem and progenitor cell (HSPC) activities; however, mechanisms regulating niche cell function are not well understood. In this study, we show that niche intrinsic expression of the CXCR4 chemokine receptor critically regulates HSPC maintenance during steady state, and promotes early hematopoietic regeneration after myeloablative irradiation. At steady state, chimeric mice with wild-type (WT) HSPC and marrow stroma that lack CXCR4 show decreased HSPC quiescence, and their repopulation capacity was markedly reduced. Mesenchymal stromal cells (MSC) were significantly reduced in the BM of CXCR4 deficient mice, which was accompanied by decreased levels of the HSPC supporting factors stromal cell-derived factor-1 (SDF-1) and stem cell factor (SCF). CXCR4 also plays a crucial role in survival and restoration of BM stromal cells after myeloablative irradiation, where the loss of BM stromal cells was more severe in CXCR4-deficient mice compared to WT mice. In addition, transplantation of WT donor HSPC into CXCR4-deficient recipient mice demonstrated reduced HSPC homing and early hematopoietic reconstitution. We found that CXCR4 signaling attenuates irradiation-induced BM stromal cell loss by upregulating the expression of the antiapoptotic protein Survivin via the PI3K pathway. Our study suggests that SDF-1-CXCR4 signaling in the stromal microenvironment cells plays a crucial role in maintenance of HSPCs during homeostasis, and promotes niche regeneration and early hematopoietic reconstitution after transplantation. Modulation of CXCR4 signaling in the HSPC microenvironment could be a means to enhance hematopoietic recovery after clinical hematopoietic cell transplantation.

Indexed as

Bone MarrowHematopoietic Stem Cell TransplantationAnimalsBone Marrow CellsChemokine CXCL12Hematopoietic Stem CellsMicePhosphatidylinositol 3-KinasesReceptors, CXCR4Transplantation ConditioningChemokine CXCL12CXCR4 protein, mousePhosphatidylinositol 3-KinasesReceptors, CXCR4

Identifiers

PMID32159901
PMCPMC7566894
OpenAlexW3012050933

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.