Title
Regional localization within the bone marrow influences the functional capacity of human HSCs
Date Issued
01 August 2013
Access level
open access
Resource Type
journal article
Author(s)
Guezguez B.
Campbell C.J.V.
Boyd A.L.
Karanu F.
Di Cresce C.
Collins T.J.
Shapovalova Z.
Xenocostas A.
Bhatia M.
McMaster Stem Cell and Cancer Research Institute
Publisher(s)
Elsevier B.V.
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. © 2013 Elsevier Inc.
Start page
175
End page
189
Volume
13
Issue
2
Language
English
OCDE Knowledge area
Biología celular, Microbiología
Scopus EID
2-s2.0-84881173663
Source
Cell Stem Cell
ISSN of the container
1934-5909
Sponsor(s)
We thank J. McNicol and J. Russell for imaging scanning and analysis assistance; David Carter (LRGC, Robarts Research Institute) for the quality of the probes and arrays; A. Fiebig-Comyn, Claudia I. Hopkins, and Monica Graham for general technical assistance; M. Levadoux-Martin for FACS analysis and cell sorting; Mary-Jo Smith for histology assistance and troubleshooting of in situ staining; and Drs. Kristin Hope, T. Ogilvie Werbowetski, and B. McIntyre for critical review of the manuscript prior to submission. We also thank members of the Labor and Delivery ward at the McMaster Children's Hospital for supplying human cord blood samples. Funding for this research was provided by a research grant from the Canadian Institutes of Health Research (CIHR) and the Ontario Cancer Research Institute (OICR). M.B. is supported by the Canadian Research Chair Program and holds a chair in human stem cell biology. B.G. designed and performed experiments, analyzed and interpreted data, and wrote manuscript draft; Z.S. performed bioinformatic and gene expression analysis; T.J.C. wrote the image processing and analysis scripts; C.J.V.C. performed experiments, analyzed and interpreted data, and edited the manuscript; F.C. and A.B. performed and assisted with the human biopsy analysis and transplant experiments; F.K. performed the Notch-HSC-related experiments; and M.B. designed the experiments, interpreted data, and wrote the manuscript.
Sources of information:
Directorio de Producción Científica
Scopus