Table 4 Skeletal stem cells and progenitors labeled by transgenes
Transgenes | Location | Features | References |
|---|---|---|---|
Prx1-Cre | Throughout limb bud mesenchyme, a subset of craniofacial mesenchyme | Prx1-Cre-expressing cells are enriched for all CFU-Fs in bone marrow | |
Sox9-Cre | Limb bud mesenchyme | Sox9-Cre-expressing cells generate cartilage, bone, tendon and synovium | |
Col2-Cre Col2-CreER Acan-CreER Sox9-CreER | Perichondrium, growth cartilage | Col2-Cre-expressing cells generate cartilage, bone, Cxcl12-abundant stromal cells, and adipocytes. Early postnatal cells marked by Col2-CreER, Acan-CreER and Sox9-CreER generate long-term progenitors in bone marrow. | |
Gli1-CreERT2 | E14.5: perichondrium 1 month: articular cartilage, upper layers of growth plate, perichondrium and chondro-osseous junction | Postnatal metaphyseal Gli1+ cells express CD146/Mcam, CD44, CD106/Vcam1, Pdgfrα, and Lepr; generate bone, stroma and adipocytes | |
Hoxa11-CreERT2 Hoxa11-EGFP | The outer periosteum and bone marrow of zeugopod | Hoxa11-expressing cells generate postnatal SSCs marked by LepR-Cre and Osx-CreER, and are PDGFRα+ and CD51+ | |
Nestin-GFP | Perichondrial and perivascular in developing bone; perivascular at adult stage | Nes-GFP marks both nonendothelial and endothelial cells, and the nonendothelial Nes+ cells are osteoblastic in developing bone. Note that Nes-Cre/Nes-CreER preferentially targets endothelial cells. Postnatal Nes-GFP+ mesenspheres are enriched for CFU-Fs; hematopoiesis-supportive. | |
Osterix-Cre Osterix-CreER | Perichondrium, growth cartilage | Osterix marks three waves of progenitors: 1. Fetal Osterix+ cells generate bone and transient stromal cells; 2. Perinatal Osterix+ cells generate bone and long-lived stromal cells (Cxcl12+, Nes-GFP+); 3. Adult Osterix+ cells contribute to osteo-lineage only. | |
PTHrP-mCherry PTHrP-CreER | Fetal stage: perichondrium Postnatal: resting zone of the growth plate | PTHrP-mCherry+ cells contain a large portion of CD45−Ter-119−Tie2−AlphaV+Thy−6C3−CD105−CD200+ mSSCs; PTHrP-expressing cells generate chondrocytes, osteoblasts and Cxcl12+ stromal cells, but not adipocytes; long-term SSCs after secondary ossification center formation | |
FoxA2-Cre | Top compartment of the resting zone of the growth plate | FoxA2+ cells are long-term and highly clonogenic; mainly contribute to the maintenance of growth plate turnover and regeneration | |
Col10a1-Cre Col10a1-CreERT2 | Growth plate hypertrophic chondrocytes | Col10a1-expressing chondrocytes undergo de-differentiation to generate long-lived SSCs | |
Pdgfrα-H2BGFP | Bone marrow | Pdgfrα+ cells are highly enriched for CFU-F, but Pdgfrα-CreER recombines poorly in bone marrow. | |
Pdgfrβ-CreERT2 | 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. | |
Gremlin1-CreERT | Primitive mesenchyme, primary spongiosa at P1, non-perivascular | Gremlin1-expressing cells give rise to osteoblasts, chondrocytes and reticular stromal cells, but not adipocytes | |
KitMerCreMer | Fetal chondrocytes, pre-osteoblasts, stromal cells | Fetal C-KIT+ cells generate ~20% postnatal LepR+ cells; KitMerCreMer does not label postnatal SSCs | |
Cxcl12-CreER | Perisinusoidal | Cxcl12-CreER-expressing cells remain quiescent physiologically, and activate to form osteoblasts in response to injury | |
LepR-Cre LepR-CreER | Perivascular | LepR+ cells are derived from fetal Col2+ cells; PDGFRα+, Prx1+, Scf-GFP+, Cxcl12-DsRedhigh, Nes-GFPlow; highly enriched for CFU-Fs; major source of bone and adipocytes in adult mice; hematopoiesis-supportive | |
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 | |
Mx1+αSMA+ (Mx1-Cre;R26-Tdt;αSMA-GFP) | Long bone and calvarial periosteum | ~80% of periosteal CD31−CD45−TER119−Mx1+αSMA+ cells are CD105+CD140a+ SSCs; highly express Runx2, Cxcl12, LepR; CCL5-medaited migration to injury site | |
Mx1-Cre | Bone marrow (Mx1-Cre labels hematopoietic cells as well) | Mx1-Cre-expressing cells label a fraction of CD105+CD140a+ SSCs; multipotent in vitro, but only give rise to osteoblasts in vivo | |
LepR+osteolectin+ Oln-mTomato OlniCreER | Periarteriolar | Almost all Oln-mTomato+ cells are LepR+; rapidly dividing, short-lived osteogenic precursors | |
Adipoq-Cre Adipoq-CreER | Bone marrow | A subpopulation of LepR+ cells; adipocytes progenitors; hematopoiesis-supportive; at least a subset of Adipoq-Cre-expressing cells are bipotent |
