Location of indigenous human HSCs reveals functional properties of HSCs that are dictated by anatomic and cellular architecture of bone marrow I

ABSTRACT: Demonstration of hematopoietic stem cells (HSCs) was first shown in the mouse and was dependent on recipient bone marrow (BM) to support in vivo multilineage hematopoietic reconstitution, thereby illustrating non-cell-autonomous requirements for HSC functions. Murine studies have defined microanatomic compartments in the BM comprised of osteoblasts, mesenchymal cells, subsets of vasculature, and innervating neural cells functioning as an HSC-supportive niche. Despite the potential clinical applications, analyses of putative HSCs in the BM of humans has not been examined. Here, using human bone biopsies, we provide evidence of HSC propensity to endosteal regions of Trabecular Bone Area (TBA). Independent of phenotypic definitions based on prospective isolation, functional studies indicate that human HSCs residing in the TBA of human and transplanted recipients had superior regenerative and self-renewal capacity and are molecularly distinct to those repopulating the Long Bone Area (LBA). Consistent with the non-cell-autonomous nature of HSC function, osteoblasts in the TBA possess unique characteristics and expressed a key network of factors including those involving Notch activity which could regulate TBA vs. LBA location of human HSCs in vivo. Our study illustrates that human-mouse xenografts provide a surrogate to indigenous human HSC in the BM, and demonstrates that BM architecture plays a critical role in defining functional properties of human HSCs. Lin- MNCs from human Umbilical Cord blood (CB) were injected via tail vein into sublethally irradiated NOD/SCID adult mice. After 10 weeks post-transplantation, engrafted-CB cells were sorted based on the co-expression of CD45 and CD34, and absence or presence of CD38 using a FACSAria II (BD). Total RNA from purified populations was extracted and amplified as described previously (Shojaei et al., 2005). Amplified-labeled RNA was hybridized to HG-U133Plus v2.0 chip.

ORGANISM(S): Homo sapiens

SUBMITTER: Mickie Bhatia 

PROVIDER: E-GEOD-47934 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress