Discoidin Domain Receptor 2(DDR2)is a collagen-activated receptor kinase that,together with integrins,is required for cells to respond to the extracellular matrix.Ddr2 loss-of-function mutations in humans and mice cau...Discoidin Domain Receptor 2(DDR2)is a collagen-activated receptor kinase that,together with integrins,is required for cells to respond to the extracellular matrix.Ddr2 loss-of-function mutations in humans and mice cause severe defects in skeletal growth and development.However,the cellular functions of Ddr2 in bone are not understood.Expression and lineage analysis showed selective expression of Ddr2 at early stages of bone formation in the resting zone and proliferating chondrocytes and periosteum.Consistent with these findings,Ddr2^(+)cells could differentiate into hypertrophic chondrocytes,osteoblasts,and osteocytes and showed a high degree of colocalization with the skeletal progenitor marker,Gli1.A conditional deletion approach showed a requirement for Ddr2 in Gli1-positive skeletal progenitors and chondrocytes but not mature osteoblasts.Furthermore,Ddr2 knockout in limb bud chondroprogenitors or purified marrow-derived skeletal progenitors inhibited chondrogenic or osteogenic differentiation,respectively.This work establishes a cell-autonomous function for Ddr2 in skeletal progenitors and cartilage and emphasizes the critical role of this collagen receptor in bone development.展开更多
Single-cell sequencing technologies have rapidly progressed in recent years,and been applied to characterize stem cells in a number of organs.Somatic(postnatal)stem cells are generally identified using combinations of...Single-cell sequencing technologies have rapidly progressed in recent years,and been applied to characterize stem cells in a number of organs.Somatic(postnatal)stem cells are generally identified using combinations of cell surface markers and transcription factors.However,it has been challenging to define micro-heterogeneity within“stem cell”populations,each of which stands at a different level of differentiation.As stem cells become defined at a single-cell level,their differentiation path becomes clearly defined.Here,this viewpoint discusses the potential synergy of single-cell sequencing analyses with in vivo lineage-tracing approaches,with an emphasis on practical considerations in stem cell biology.展开更多
基金supported by a scholarship from the Ministry of Higher Education and Scientific Research, Libyan Transitional Government (FFM)a scholarship from King Saud University (AB), NIH/NIDCR grants DE11723, DE029012, DE029465+1 种基金Department of Defense grant PR190899, research funds from the Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry (to RTF)the Michigan Musculoskeletal Health Core Center ((NIH/NIAMS P30 AR069620)
文摘Discoidin Domain Receptor 2(DDR2)is a collagen-activated receptor kinase that,together with integrins,is required for cells to respond to the extracellular matrix.Ddr2 loss-of-function mutations in humans and mice cause severe defects in skeletal growth and development.However,the cellular functions of Ddr2 in bone are not understood.Expression and lineage analysis showed selective expression of Ddr2 at early stages of bone formation in the resting zone and proliferating chondrocytes and periosteum.Consistent with these findings,Ddr2^(+)cells could differentiate into hypertrophic chondrocytes,osteoblasts,and osteocytes and showed a high degree of colocalization with the skeletal progenitor marker,Gli1.A conditional deletion approach showed a requirement for Ddr2 in Gli1-positive skeletal progenitors and chondrocytes but not mature osteoblasts.Furthermore,Ddr2 knockout in limb bud chondroprogenitors or purified marrow-derived skeletal progenitors inhibited chondrogenic or osteogenic differentiation,respectively.This work establishes a cell-autonomous function for Ddr2 in skeletal progenitors and cartilage and emphasizes the critical role of this collagen receptor in bone development.
基金This research was supported by National Institute of Health Grants R01DE026666 and R01DE030630(to NO)and R01DE029181(to WO).
文摘Single-cell sequencing technologies have rapidly progressed in recent years,and been applied to characterize stem cells in a number of organs.Somatic(postnatal)stem cells are generally identified using combinations of cell surface markers and transcription factors.However,it has been challenging to define micro-heterogeneity within“stem cell”populations,each of which stands at a different level of differentiation.As stem cells become defined at a single-cell level,their differentiation path becomes clearly defined.Here,this viewpoint discusses the potential synergy of single-cell sequencing analyses with in vivo lineage-tracing approaches,with an emphasis on practical considerations in stem cell biology.
