2020
DOI: 10.1016/j.stemcr.2020.03.001
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C-KIT Expression Distinguishes Fetal from Postnatal Skeletal Progenitors

Abstract: Hematopoietic stem cells (HSCs) and skeletal stem cells (SSCs) cohabit in the bone marrow. KITL (C-KIT ligand) from LEPR + adult bone marrow stromal cells is pivotal for HSC maintenance. In contrast, it remains unclear whether KITL/C-KIT signaling also regulates SSCs.Here, we lineage traced C-KIT + cells and found that C-KIT was expressed by fetal, but not postnatal skeletal progenitors. Fetal C-KIT + cells gave rise to 20% of LEPR + stromal cells in adult bone marrow, forming nearly half of all osteoblasts. D… Show more

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Cited by 8 publications
(9 citation statements)
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References 45 publications
(57 reference statements)
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“…There exists a difference in the types of MSCs in the embryonic period and after birth. 32 , 33 The results indicate the heterogeneity of MSCs of molars, a finding similar to that reported recently in bone development, which stated that bone formation before and after adolescence is controlled by distinct progenitors. 34 In addition, the heterogeneity of MSCs is related to the location of their origin.…”
Section: Discussionsupporting
confidence: 87%
“…There exists a difference in the types of MSCs in the embryonic period and after birth. 32 , 33 The results indicate the heterogeneity of MSCs of molars, a finding similar to that reported recently in bone development, which stated that bone formation before and after adolescence is controlled by distinct progenitors. 34 In addition, the heterogeneity of MSCs is related to the location of their origin.…”
Section: Discussionsupporting
confidence: 87%
“… 61 , 64 Pdgfrβ-Cre ERT2 Metaphysis, bone marrow, periosteum, a small fraction of growth plate cartilage Perinatal Pdgfrβ + cells are restricted to metaphysis, and juvenile Pdgfrβ + cells are located at metaphysis and bone marrow; Pdgfrβ + cells generate osteoprogenitors, chondrocytes and adipocytes; Pdgfrα + β + metaphyseal SSCs generate diaphyseal SSCs. 137 Gremlin1-Cre ERT Primitive mesenchyme, primary spongiosa at P1, non-perivascular Gremlin1-expressing cells give rise to osteoblasts, chondrocytes and reticular stromal cells, but not adipocytes 97 Kit MerCreMer Fetal chondrocytes, pre-osteoblasts, stromal cells Fetal C-KIT + cells generate ~20% postnatal LepR + cells; Kit MerCreMer does not label postnatal SSCs 118 Cxcl12-Cre ER Perisinusoidal Cxcl12-Cre ER -expressing cells remain quiescent physiologically, and activate to form osteoblasts in response to injury 123 LepR-Cre LepR-Cre ER Perivascular LepR + cells are derived from fetal Col2 + cells; PDGFRα + , Prx1 + , Scf -GFP + , Cxcl12-DsRed high , Nes -GFP low ; highly enriched for CFU-Fs; major source of bone and adipocytes in adult mice; hematopoiesis-supportive 64 , 77 CTSK- mGFP Ctsk-Cre Long bone and calvarial periosteum (endosteal CTSK- mGFP cells are osteoclasts) Periosteal CTSK-mGFP + cells contain TER119 - CD31 − CD45 − THY1.2 − 6C3 − CD200 + CD105 − mSSCs; bone formation via intramembranous ossification physiologically; re-establish endochondral bone formation ability in response to injury 71 Mx1 + αSMA + ( Mx1-Cre;R26-Tdt;αSMA -GFP) Long bone and calvarial periosteum ...…”
Section: Skeletal Stem Cells In Long Bonesmentioning
confidence: 99%
“… 117 One interesting finding is the C-KIT + mesenchymal cells. 118 C-KIT ligand/C-KIT signaling is known to maintain HSCs in bone marrow. Postnatal C-KIT + cells did not mark osteoblasts or adipocytes, but fetal C-KIT + progenitors gave rise to bone and bone marrow stroma.…”
Section: Skeletal Stem Cells In Long Bonesmentioning
confidence: 99%
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“…In preclinical models, platelet-derived growth factor receptor, but above all c-KIT, two well-known targets of sunitinib, play a key role in bone formation, homeostasis of mesenchymal stem cell, and differentiation into osteogenesis progenitors. We hypothesize that in healing scars, sunitinib exposure modified the mesenchymal stem cell differentiation regulation into osteoblast-like cells [ 9 14 ]. Another hypothesis is that sunitinib alters mitochondria functions.…”
Section: Discussionmentioning
confidence: 99%