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Cited by 20Hematopoietic Stem Cell TransplantationBlood disorders and treatmentsMesenchymal stem cell research

The Wave2 scaffold Hem-1 is required for transition of fetal liver hematopoiesis to bone marrow

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Shao, Lijian, Chang, Jianhui, Feng, Wei, Wang, Xiaoyan, Williamson, Elizabeth A., Li, Ying, Schajnovitz, Amir, Scadden, David +7 more·2018·Nature Communications
DOI 10.1038/s41467-018-04716-5PMC PMC6006146
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Abstract

The transition of hematopoiesis from the fetal liver (FL) to the bone marrow (BM) is incompletely characterized. We demonstrate that the Wiskott–Aldrich syndrome verprolin-homologous protein (WAVE) complex 2 is required for this transition, as complex degradation via deletion of its scaffold Hem-1 causes the premature exhaustion of neonatal BM hematopoietic stem cells (HSCs). This exhaustion of BM HSC is due to the failure of BM engraftment of Hem-1−/− FL HSCs, causing early death. The Hem-1−/− FL HSC engraftment defect is not due to the lack of the canonical function of the WAVE2 complex, the regulation of actin polymerization, because FL HSCs from Hem-1−/− mice exhibit no defects in chemotaxis, BM homing, or adhesion. Rather, the failure of Hem-1−/− FL HSC engraftment in the marrow is due to the loss of c-Abl survival signaling from degradation of the WAVE2 complex. However, c-Abl activity is dispensable for the engraftment of adult BM HSCs into the BM. These findings reveal a novel function of the WAVE2 complex and define a mechanism for FL HSC fitness in the embryonic BM niche.

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  • Defects in neutrophil, dendritic cell, and macrophage migration and phagocytosis impair innate immune defenses, predisposing HEM1-deficient patients to bacterial infections.

    “Like mouse models of HEM1 deficiency, defects in neutrophil, dendritic cell, and macrophage migration and phagocytosis impair innate immune defenses, predisposing patients to bacterial infections [32–35].”

    From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [34]

    The Results section ‘Hem-1−/− FL HSCs can migrate to the BM’ (page unavailable) reports defective migration in neutrophils from Hem-1-deficient mice. It does not establish migration or phagocytosis defects in dendritic cells or macrophages, or show that these defects predispose HEM1-deficient patients to bacterial infections. (LLM, conf=0.88)

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Authors
Shao, L., Chang, J., Feng, W., Wang, X., Williamson, E. A., Li, Y., Schajnovitz, A., Scadden, D., Mortensen, L. J., Lin, C. P., Li, L., Paulson, A., Downing, J., Zhou, D., & Hromas, R. A.
Affiliations
  • University of Illinois Chicago (US)
  • University of Arkansas for Medical Sciences (US)
  • University of Florida (US)
  • Harvard University (US)
  • University of Georgia (US)
  • University of Kansas (US)
  • Stowers Institute for Medical Research (US)
  • St. Jude Children's Research Hospital (US)
  • The University of Texas at San Antonio Health Science Center (US)
Corresponding author
  • Zhou, Daohong
  • Hromas, Robert A.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-06-18
Volume
9
Issue
1
Pages
2377-2377
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-04716-5
PMC
PMC6006146
OpenAlex
W2808234044
Cited by
20
References
2
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2022: 5 · 2021: 3 · 2020: 6 · 2019: 2
FWCI
1.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
U.S. Department of Health & Human Services | National Institutes of Health (AI080421, CA122023, P20GM109005, GM109645, CA139429)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
fetal liver hematopoiesis, bone marrow hematopoiesis, hematopoietic stem cells, HSC engraftment, actin polymerization
MeSH terms
Animals, Bone Marrow, Cell Movement, Cytoskeletal Proteins, Hematopoiesis, Hematopoietic Stem Cells, Liver, Male, Mice, Inbred C57BL, Mice, Transgenic, Proto-Oncogene Proteins c-abl, Fetal Development, Adaptor Proteins, Signal Transducing, Wiskott-Aldrich Syndrome Protein Family

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