Phenotypically identical hemopoietic stem cells isolated from different regions of bone marrow have different biologic potential.
Hemopoietic stem cells (HSCs) reside within a specified area of the bone marrow (BM) cavity called a "niche" that modulates HSC quiescence, proliferation, differentiation, and migration. Our previous studies have identified the endosteal BM region as the site for the HSC niche and demonstrated that hemopoietic stem and progenitor populations (HSPCs, LSK) isolated from different BM regions exhibit significantly different hemopoietic potential. In this study, we have analyzed subpopulations of LSK cells isolated from different regions of the BM and showed that CD150(+)CD48(-)LSK HSCs within the endosteal BM region have superior proliferative capacity and homing efficiency compared with CD150(+)CD48(-)LSK HSCs isolated from the central BM. Furthermore, we show, for the first time, that a subset of CD150(+)CD48(+)LSK progenitor cells, previously defined as B-lymphoid primed hemopoietic cells, are capable of multilineage reconstitution, however, only when isolated from the endosteal region. In addition, we provide evidence for an unrecognized role of CD48 in HSC homing. Together, our data provide strong evidence that highly purified HSCs show functional differences depending on their origin within the BM and that the most primitive HSCs reside within the endosteal BM region.
Grassinger
Jochen
J
Australian Stem Cell Centre, Monash University, Wellington Rd., Clayton, Victoria 3800, Australia.
Haylock
David N
DN
Williams
Brenda
B
Olsen
Gemma H
GH
Nilsson
Susan K
SK
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000950:Antigens, Ly / Q000378:metabolism; D001853:Bone Marrow / Q000033:anatomy & histology*; D000071178:CD48 Antigen; D002453:Cell Cycle; D049109:Cell Proliferation; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
D015703:Antigens, CD; D000950:Antigens, Ly; D000071178:CD48 Antigen; C000604066:Cd48 protein, mouse; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D019009:Proto-Oncogene Proteins c-kit