Identification of a common mesenchymal stromal progenitor for the adult haematopoietic niche

Xingbin Hu, Mayra Garcia, Lihong Weng, Xiaoman Jung, Jodi L. Murakami, Bijender Kumar, Charles D. Warden, Ivan Todorov and Ching-Cheng Chen ()
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Xingbin Hu: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope
Mayra Garcia: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope
Lihong Weng: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope
Xiaoman Jung: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope
Jodi L. Murakami: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope
Bijender Kumar: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope
Charles D. Warden: Bioinformatics Core, Beckman Research Institute of City of Hope
Ivan Todorov: Beckman Research Institute of City of Hope
Ching-Cheng Chen: Divison of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute of City of Hope

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13095

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