title: Identification of a common mesenchymal stromal progenitor for the adult haematopoietic niche.
abstract: Microenvironment cues received by haematopoietic stem cells (HSC) are important in regulating the choice between self-renewal and differentiation. On the basis of the differential expression of cell-surface markers, here we identify a mesenchymal stromal progenitor hierarchy, where CD45-Ter119-CD31-CD166-CD146-Sca1+(Sca1+) progenitors give rise to CD45-Ter119-CD31-CD166-CD146+(CD146+) intermediate and CD45-Ter119-CD31-CD166+CD146-(CD166+) mature osteo-progenitors. All three progenitors preserve HSC long-term multi-lineage reconstitution capability in vitro; however, their in vivo fates are different. Post-transplantation, CD146+and CD166+progenitors form bone only. While Sca1+progenitors produce CD146+, CD166+progenitors, osteocytes and CXCL12-producing stromal cells. Only Sca1+progenitors are capable of homing back to the marrow post-intravenous infusion. Ablation of Sca1+progenitors results in a decrease of all three progenitor populations as well as haematopoietic stem/progenitor cells. Moreover, suppressing production of KIT-ligand in Sca1+progenitors inhibits their ability to support HSCs. Our results indicate that Sca1+progenitors, through the generation of both osteogenic and stromal cells, provide a supportive environment for hematopoiesis.
authors.affiliation: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.|Department of Transfusion Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 7100032, PR China.
authors.forename: Xingbin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
authors.forename: Mayra
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
authors.forename: Lihong
authors.initials: L
authors.lastname: Weng
authors.affiliation: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Jung
authors.affiliation: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.|Irell &Manella Graduate School of Biological Sciences, City of Hope, Duarte, California 91010, USA.
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Murakami
authors.affiliation: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
authors.forename: Bijender
authors.initials: B
authors.lastname: Kumar
authors.affiliation: Bioinformatics Core, Department of Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Warden
authors.affiliation: Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Todorov
authors.affiliation: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.|Irell &Manella Graduate School of Biological Sciences, City of Hope, Duarte, California 91010, USA.
authors.forename: Ching-Cheng
authors.initials: CC
authors.lastname: Chen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D001842:Bone and Bones / Q000166:cytology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006410:Hematopoiesis; D007275:Injections, Intravenous; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008810:Mice, Inbred C57BL; D010641:Phenotype; D019089:Stem Cell Factor / Q000378:metabolism; D055153:Stem Cell Niche; D017154:Stromal Cells / Q000166:cytology
chemical_list: D015703:Antigens, CD; D019089:Stem Cell Factor; D049452:Green Fluorescent Proteins