title: Enhanced Hematopoietic Stem Cell Self-Renewal-Promoting Ability of Clonal Primary Mesenchymal Stromal/Stem cells Versus Their Osteogenic Progeny.
abstract: Long-term self-renewing hematopoietic stem cell (LT-HSC) homeostasis within the bone marrow (BM) of adult mammals is regulated by complex interactions between LT-HSC and a number of niche-associated cell types including mesenchymal stromal/stem cells (MSC), osteoblasts (OB), macrophage, and neuronal cells in close proximity with the vasculature. Here, we cloned and functionally characterized a murine BM MSC subpopulation that was uniformly Nestin+Lepr+Sca-1+CD146+and could be stably propagated with high colony-forming unit fibroblast re-cloning efficiency. MSC synergized with SCF and IL-11 to support a 20-fold expansion in true LT-HSC after 10-days of in vitro coculture. Optimal stimulation of LT-HSC expansion was minimally dependent on Notch signaling but was significantly enhanced by global inhibition of Wnt signaling. The self-renewal-promoting activity of MSC was progressively lost when MSC clones were differentiated into mature OB. This suggests that the stage of osteoblast development may significantly impact the ability of osteolineage cells to support LT-HSC homeostasis in vivo. Stem Cells 2017;35:473-484.
authors.affiliation: Department of Microbiology, University of Alabama-Birmingham, Alabama, USA.
authors.forename: Qiling
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Microbiology, University of Alabama-Birmingham, Alabama, USA.
authors.forename: Claude
authors.initials: C
authors.lastname: Scott Swindle
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, P.R. China.|School of Biomedical Sciences Core Laboratory, Institute of Stem Cell, Genomics and Translational Research, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wan
authors.affiliation: Department of Microbiology, University of Alabama-Birmingham, Alabama, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Flynn
authors.affiliation: Division of Preventative Medicine, University of Alabama-Birmingham, Alabama, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Oster
authors.affiliation: Division of Preventative Medicine, University of Alabama-Birmingham, Alabama, USA.
authors.forename: Dongquan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Fengjie
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Yinglan
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of Microbiology, University of Alabama-Birmingham, Alabama, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Klug
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D000066673:Cell Self Renewal; D002478:Cells, Cultured; D002999:Clone Cells; D018920:Coculture Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008810:Mice, Inbred C57BL; D009999:Ossification, Heterotopic / Q000473:pathology; D010012:Osteogenesis; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051880:Receptors, Notch
keywords: Adult haematopoietic stem cells; Bone marrow stromal cells; Hemopoietic stem cells; Mesenchymal stem cells; Notch; Self-renewal; Wnt