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Cell Rep. 2019 Jan 15;26(3):652-669.e6. doi: 10.1016/j.celrep.2018.12.093.

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

Author information

1
Institute of Hematology, the Third Affiliated Hospital of Sun Yat-Sen University; Key Laboratory of Stem Cells and Tissue Engineering Sun Yat-Sen University, Guangzhou 510000, China; Stowers Institute for Medical Research, Kansas City, MO 66110, USA.
2
Stowers Institute for Medical Research, Kansas City, MO 66110, USA; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
3
Stowers Institute for Medical Research, Kansas City, MO 66110, USA.
4
Stowers Institute for Medical Research, Kansas City, MO 66110, USA; Center of Stem Cell and Regenerative Medicine, Institute of Hematology, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China 310058.
5
Stowers Institute for Medical Research, Kansas City, MO 66110, USA; Children's Research Institute, Children's Mercy, Kansas City, MO 64108, USA.
6
Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, KS 66160, USA.
7
Stowers Institute for Medical Research, Kansas City, MO 66110, USA; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: lil@stowers.org.

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.

KEYWORDS:

MSC; N-cadherin; endosteum; niche; reserve stem cell; stress response

PMID:
30650358
DOI:
10.1016/j.celrep.2018.12.093
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