Human osteogenic progenitors are not precisely defined,being primarily studied as heterogeneous multipotent cell populations and termed mesenchymal stem cells(MSCs).Notably,select human pericytes can develop into bone...Human osteogenic progenitors are not precisely defined,being primarily studied as heterogeneous multipotent cell populations and termed mesenchymal stem cells(MSCs).Notably,select human pericytes can develop into bone-forming osteoblasts.Here,we sought to define the differentiation potential of CD146 f human pericytes from skeletal and soft tissue sources,with the underlying goal of defining cell surface markers that typify an osteoblastogenic pericyte.CD146+CD31~CD45_pericytes were derived by fluorescence-activated cell sorting from human periosteum,adipose,or dermal tissue.Periosteal CD146+CD31—CD45 cells retained canonical features of pericytes/MSC.Periosteal pericytes demonstrated a striking tendency to undergo osteoblastogenesis in vitro and skeletogenesis in vivo,while soft tissue pericytes did not readily.Transcriptome analysis revealed higher CXCR4 signaling among periosteal pericytes in comparison to their soft tissue counterparts,and CXCR4 chemical inhibition abrogated ectopic ossification by periosteal pericytes.Conversely,enrichment of CXCR4+pericytes or stromal cells identified an osteoblastic/non-adipocytic precursor cell.In sum,human skeletal and soft tissue pericytes differ in their basal abilities to form bone.Diversity exists in soft tissue pericytes,however,and CXCR4+pericytes represent an osteoblastogenic,non-adipocytic cell precursor.Indeed,enrichment for CXCR4-expressing stromal cells is a potential new tactic for skeletal tissue engineering.展开更多
基金A.WJ.was supported by the NIH/NIAMS(R01 AR070773,K08 AR068316),NIH/NIDCR(R21 DE027922)Department of Defense(W81XWH-18-1-0121,W81XWH-18-1-0336,W81XWH-18-10613)+1 种基金American Cancer Society(Research Scholar Grant,RSG-18-027-01-CSM)the Maryland Stem Cell Research Foundation,and the Musculoskeletal Transplant Foundation.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health,Department of Defense,or US Army.We thank the JHU microscopy facility,JHMI deep sequencing and microarray core facility,and Hao Zhang within the JHU Bloomberg Flow Cytometry and Immunology Core for their technical assistance.
文摘Human osteogenic progenitors are not precisely defined,being primarily studied as heterogeneous multipotent cell populations and termed mesenchymal stem cells(MSCs).Notably,select human pericytes can develop into bone-forming osteoblasts.Here,we sought to define the differentiation potential of CD146 f human pericytes from skeletal and soft tissue sources,with the underlying goal of defining cell surface markers that typify an osteoblastogenic pericyte.CD146+CD31~CD45_pericytes were derived by fluorescence-activated cell sorting from human periosteum,adipose,or dermal tissue.Periosteal CD146+CD31—CD45 cells retained canonical features of pericytes/MSC.Periosteal pericytes demonstrated a striking tendency to undergo osteoblastogenesis in vitro and skeletogenesis in vivo,while soft tissue pericytes did not readily.Transcriptome analysis revealed higher CXCR4 signaling among periosteal pericytes in comparison to their soft tissue counterparts,and CXCR4 chemical inhibition abrogated ectopic ossification by periosteal pericytes.Conversely,enrichment of CXCR4+pericytes or stromal cells identified an osteoblastic/non-adipocytic precursor cell.In sum,human skeletal and soft tissue pericytes differ in their basal abilities to form bone.Diversity exists in soft tissue pericytes,however,and CXCR4+pericytes represent an osteoblastogenic,non-adipocytic cell precursor.Indeed,enrichment for CXCR4-expressing stromal cells is a potential new tactic for skeletal tissue engineering.
