TY - JOUR
T1 - Regional localization within the bone marrow influences the functional capacity of human HSCs
AU - Guezguez, Borhane
AU - Campbell, Clinton J.V.
AU - Boyd, Allison L.
AU - Karanu, Francis
AU - Casado, Fanny L.
AU - Di Cresce, Christine
AU - Collins, Tony J.
AU - Shapovalova, Zoya
AU - Xenocostas, Anargyros
AU - Bhatia, Mickie
PY - 2013/8/1
Y1 - 2013/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84881173663&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2013.06.015
DO - 10.1016/j.stem.2013.06.015
M3 - Article
AN - SCOPUS:84881173663
SN - 1934-5909
VL - 13
SP - 175
EP - 189
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 2
ER -