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Cited by 146Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchBlood disorders and treatments

N-Cadherin-Expressing Bone and Marrow Stromal Progenitor Cells Maintain Reserve Hematopoietic Stem Cells

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Zhao, Meng, Tao, Fang, Venkatraman, Aparna, Li, Zhenrui, Smith, Sarah E., Unruh, Jay, Chen, Shiyuan, Ward, Christina +6 more·2019·Cell Reports
DOI 10.1016/j.celrep.2018.12.093PMC PMC6890378
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Abstract

Regulation of hematopoietic stem cells (HSCs) by bone marrow (BM) niches has been extensively studied; however, whether and how HSC subpopulations are distinctively regulated by BM niches remain unclear. Here, we functionally distinguished reserve HSCs (rHSCs) from primed HSCs (pHSCs) based on their response to chemotherapy and examined how they are dichotomously regulated by BM niches. Both pHSCs and rHSCs supported long-term hematopoiesis in homeostasis; however, pHSCs were sensitive but rHSCs were resistant to chemotherapy. Surviving rHSCs restored the HSC pool and supported hematopoietic regeneration after chemotherapy. The rHSCs were preferentially maintained in the endosteal region that enriches N-cadherin + (N-cad + ) bone-lining cells in homeostasis and post-chemotherapy. N-cad + cells were functional bone and marrow stromal progenitor cells (BMSPCs), giving rise to osteoblasts, adipocytes, and chondrocytes in vitro and in vivo . Finally, ablation of N-cad + niche cells or deletion of SCF from N-cad + niche cells impaired rHSC maintenance during homeostasis and regeneration.

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  • HSCLT-enriched SLAM cells overlap phenotypically with deeply quiescent CD49blo reserve HSCs and remain almost exclusively in a quiescent (G0) cell cycle state despite chronic IL-1 exposure.

    “We previously showed that HSCLT-enriched SLAM cells (defined as LSK/Flk2−CD48−CD150+CD34−EPCR+; Fig. S1 E) overlap phenotypically with deeply quiescent CD49blo reserve HSCs (Zhao et al., 2019) and remain almost exclusively in a quiescent (G0) cell cycle state, despite chronic IL-1 exposure (Rabe et al., 2020).”

    From PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress (2021) · cites this paper as Zhao et al., 2019

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Authors
Zhao, M., Tao, F., Venkatraman, A., Li, Z., Smith, S. E., Unruh, J., Chen, S., Ward, C., Qian, P., Perry, J. M., Marshall, H., Wang, J., He, X. C., & Li, L.
Affiliations
  • Stowers Institute for Medical Research (US)
  • University of Kansas Medical Center (US)
Corresponding author
Li, Linheng
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2019-01
Volume
26
Issue
3
Pages
652-669.e6
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2018.12.093
PMC
PMC6890378
OpenAlex
W2910574111
Cited by
146
References
7
Citations by year
2026: 8 · 2025: 9 · 2024: 20 · 2023: 19 · 2022: 23 · 2021: 24 · 2020: 28 · 2019: 15
FWCI
15.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Key Research
  • Development Program of China (2017YFA0103403, 2018YFA0107203)
  • Department of Biotechnology
  • Ministry of Science and Technology
  • Government of India
  • NIH (R01 AR05988, R01 DE018713)
  • Stowers Institute for Medical Research funding (SIMR-1004)
  • NIH National Cancer Institute Cancer Center (P30 CA168524)
  • University of Kansas Cancer Center
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
Keywords
N-cadherin, mesenchymal stem cells, hematopoietic stem cells, hematopoietic stem cell maintenance, hematopoietic niche, niche cells
MeSH terms
Hematopoietic Stem Cells, Humans, Stem Cells, Cadherins, Stromal Cells

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