Regional Localization within the Bone Marrow Influences the Functional Capacity of Human HSCs

被引：87

作者：

Guezguez, Borhane ^{[1
]}

Campbell, Clinton J. V. ^{[1
,2
]}

Boyd, Allison L. ^{[1
,2
]}

Karanu, Francis ^{[1
]}

Casado, Fanny L. ^{[1
]}

Di Cresce, Christine ^{[3
,4
]}

Collins, Tony J. ^{[1
]}

Shapovalova, Zoya ^{[1
]}

Xenocostas, Anargyros ^{[5
,6
]}

Bhatia, Mickie ^{[1
,2
]}

机构：

[1] McMaster Univ, Michael G DeGroote Sch Med, McMaster Stem Cell & Canc Res Inst, Hamilton, ON L8N 3Z5, Canada

[2] McMaster Univ, Dept Biochem, Hamilton, ON L8N 3Z5, Canada

[3] Univ Western Ontario, Lawson Hlth Res Inst, London, ON N6A 5C1, Canada

[4] Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6A 5C1, Canada

[5] Univ Western Ontario, London Hlth Sci Ctr, London, ON N6A 5C1, Canada

[6] Univ Western Ontario, Schulich Sch Med, London, ON N6A 5C1, Canada

来源：

CELL STEM CELL | 2013年 / 13卷 / 02期

基金：

加拿大健康研究院;

关键词：

HEMATOPOIETIC STEM-CELL; CORD BLOOD TRANSPLANTATION; NOTCH LIGAND JAGGED1; NOD-SCID MICE; PROGENITOR CELLS; SELF-RENEWAL; INTRAFEMORAL TRANSPLANTATION; MURINE BONE; IN-VIVO; NICHE;

D O I：

10.1016/j.stem.2013.06.015

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：175 / 189

页数：15

共 73 条

[1] Therapeutic targeting of a stem cell niche [J].