title: Regional localization within the bone marrow influences the functional capacity of human HSCs.
abstract: Numerous studies have shown that the bone marrow (BM) niche plays a key role in mouse hematopoietic stem cell (HSC) function and involves contributions from a broad array of cell types. However, the composition and role of the human BM HSC niche have not been investigated. Here, using human bone biopsy specimens, we provide evidence of HSC propensity to localize to endosteal regions of the trabecular bone area (TBA). Through functional xenograft transplantation, we found that human HSCs localizing to the TBA have superior regenerative and self-renewal capacity and are molecularly distinct from those localizing to the long bone area (LBA). In addition, osteoblasts in the TBA possess unique characteristics and express a key network of factors that regulate TBA- versus LBA-localized human HSCs in vivo. Our study reveals that BM localization and architecture play a critical role in defining the functional and molecular properties of human HSCs.
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
authors.forename: Borhane
authors.initials: B
authors.lastname: Guezguez
authors.forename: Clinton J V
authors.initials: CJ
authors.lastname: Campbell
authors.forename: Allison L
authors.initials: AL
authors.lastname: Boyd
authors.forename: Francis
authors.initials: F
authors.lastname: Karanu
authors.forename: Fanny L
authors.initials: FL
authors.lastname: Casado
authors.forename: Christine
authors.initials: C
authors.lastname: Di Cresce
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Collins
authors.forename: Zoya
authors.initials: Z
authors.lastname: Shapovalova
authors.forename: Anargyros
authors.initials: A
authors.lastname: Xenocostas
authors.forename: Mickie
authors.initials: M
authors.lastname: Bhatia
mesh_terms: D000818:Animals; D001706:Biopsy; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D001842:Bone and Bones / Q000473:pathology*; D049109:Cell Proliferation; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008024:Ligands; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D051880:Receptors, Notch / Q000378:metabolism; D055153:Stem Cell Niche; D023041:Xenograft Model Antitumor Assays
chemical_list: D008024:Ligands; D051880:Receptors, Notch