Table 1. Summary of recent lineage tracing studies of pre- and mature adipocytes.
Genetic approach | Promoter location1 |
Rationale | Reported result2 | References3 | |
---|---|---|---|---|---|
White
adipocytes |
sox10-Cre;
R26R-eYFP |
Transgene | Sox10 expresses in pre- and migratory neural crest cells at all rostro-caudal levels |
Mature adipocytes in the salivary gland labeled positive; pgWAT and ingWAT labeled negative |
[103, 139] |
PPARγ-tTA;TRE-Cre;
R26R-LacZ |
Knock-in | PPARγ is a nuclear receptor expressed in all tissues and is critical for adipogenesis |
IngWAT and rWAT positive; some positive SVF cells | [82] | |
aP2-GFP | Transgene | aP2 (FABP4) expresses in mature adipocytes and is a target of PPARγ |
ingWAT positive | [82] | |
aP2-Cre;R26R-LacZ | Transgene | Described above | ingWAT and pgWAT positive | [82] | |
PDGFRβ-Cre;
R26R-LacZ |
Transgene | PDFGRβ is expressed in vascular mural cells | ingWAT and rWAT positive | [82, 140] | |
myf5-Cre;
R26R-eYFP |
Knock-in | Myf5 is a muscle differentiation transcription factor that is first expressed in the dermomyotome at E8.0 and expresses in adult satellite cells |
ingWAT and pgWAT negative | [116, 117] | |
wnt1-Cre;
R26R-eYFP |
Transgene | Restrictive marker of migrating neural crest cells | Cephalic WAT positive; pgWAT and ingWAT negative. 70% of adipocyte precursors in cephalic WAT positive; all ingWAT adipocyte precursors negative |
[104, 141] | |
LysM-Cre;
R26R-LacZ |
Knock-in | The lysozyme M is exclusively expressed in macrophages and granulocytes |
5-20% of pgWAT adipocytes positive | [110, 111] | |
VE-cadherin-Cre; R26R-LacZ |
Knock-in | VE-cadherin is expressed in endothelial cells, is involved in cell adhesion, and is essential for vascular system development |
ingWAT and pgWAT positive | [96, 98] | |
VE-cadherin-Cre;
R26R-eGFP |
Knock-in | Described above | Subset of mature adipocytes in the pgWAT positive | [96, 98] | |
VE-cadherin-CreERT2;
R26R-LacZ |
Knock-in | VE-cadherin-CreERT2 is a tamoxifen-inducible version of the VE-cadherin-Cre |
Numerous adipocytes in the ingWAT, pgWAT and BAT positive |
[97, 98] | |
ZFP423-GFP | Knock-in | Zfp423 is a transcriptional regulator broadly expressed but essential for preadipocyte commitment |
ingWAT positive | [95] | |
pax3-Cre;
R26R-mTmG |
Knock-in | Pax3 is a muscle differentiation transcription factor first expressed in dorsal neural crest and somites; it cooperates with Myf5 to drive muscle development |
50% of the adipogenic SVF cells from asWATs positive |
[123, 124] | |
myf5-Cre;R26R-LacZ | Knock-in | Described above | Mature adipocytes from asWATs and rWAT positive; Few mature adipocytes from ingWAT and pgWAT positive; 50-60% of adipogenic SVF cells from asWAT and rWAT positive; <2% from the ingWAT and pgWAT positive |
[83, 117] | |
myf5-Cre;R26R-eYFP | Knock-in | Described above | 50-70% of the adipocyte precursors from asWATs and rWAT positive; <10% of the adipocyte precursors from pgWAT and ingWAT positive |
[83, 117] | |
vav1-Cre;
R26R-mTmG |
Knock-in | Vav1 is a proto-oncogene that expresses in the hematopoietic and lymphoid systems |
All adipocyte precursors and mature adipocytes from ingWAT, pgWAT, rWAT and mWAT negative |
[100, 112] | |
tie2-Cre;R26R-mTmG | Transgene | Tie2 is an angiopoietin receptor specific to endothelial cells and some hematopoietic cells |
All adipocyte precursors and mature adipocytes from ingWAT, pgWAT, rWAT and mWAT negative |
[100, 142] | |
VE-cadherin-Cre;
R26R-mTmG |
Knock-in | Described above | All adipocyte precursors and mature adipocytes from ingWAT, pgWAT, rWAT and mWAT negative |
[96, 100] | |
PDFGRα-Cre;
R26R-mTmG |
Transgene | PDGFRα is expressed in most mesenchymal cells can activate the MAPK, PI3K and PLCγ signaling pathways |
All adipocyte precursors and mature adipocytes from ingWAT, pgWAT, rWAT and mWAT positive |
[100, 143] | |
Brown
adipocytes |
En1-Cre;R26R-LacZ | Knock-in | Engrailed 1 is a homeobox transcription factor that expresses in cells of the central dermomyotome |
BAT positive | [114, 144] |
myf5-Cre;R26R-eYFP | Knock-in | Described above | BAT positive | [116, 117] | |
pax7-CreERT2; R26R-LacZ |
Knock-in | Pax7 is expressed in medial and central cells of the dermomyotome and in adult satellite cells |
BAT positive | [121, 122] | |
pax3-cre;R26R-mTmG | Knock-in | Described above | All adipogenic cells from the SVF of BAT positive | [123, 124] | |
myf5-Cre;R26R-LacZ | Knock-in | Described above | BAT positive; >99% of adipogenic BAT SVF cells positive |
[83, 117] | |
myf5-Cre;R26R-eYFP | Knock-in | Described above | >95% of BAT adipocyte precursors positive | [83, 117] | |
VE-cadherin- Cre;R26R-LacZ |
Knock-in | Described above | BAT positive | [96, 98] | |
VE-cadherin-CreERT2;
R26R-LacZ |
Knock-in | Described above | Many brown adipocytes positive | [97, 98] | |
Brite
adipocytes |
myf5-Cre;R26R-eYFP | Knock-in | Described above | Brite adipocytes in ingWAT negative | [116, 117] |
PDGFRα-CreERT2;
R26R-tdTomato |
Knock-in |
PDGFRα-CreERT2 is a tamoxifen-inducible version of the PDGFRα-CreER |
90% of the CL316,243 induced brite adipocytes in pgWAT positive |
[50, 145] | |
myf5-Cre;R26R-LacZ | Knock-in | Described above | CL316,243 induced brite adipocytes in asWATs and rWAT positive; brite adipocytes induced in ingWAT negative |
[83, 117] | |
VE-cadherin-CreERT2;
R26R-LacZ |
Knock-in | Described above | Rosiglitazone induced bright adipocytes in ingWAT positive |
[97, 98] | |
UCP1-CreERT2;
R26R-tdRFP |
Knock-in | UCP1 is the most accepted functional marker of brown adipocytes |
Brite and white adipocytes interconverts in ingWAT depending on the temperature |
[51] | |
Adipocyte
precursors in skeletal muscle |
myf5-Cre;R26R-eYFP | Knock-in | Described above | negative | [84, 117] |
myf5-Cre;R26R-eYFP | Knock-in | Described above | negative | [37, 117] | |
myf5-Cre;R26R-mTmG | Knock-in | Described above | negative | [117, 124] | |
Pax3-Cre; R26R- mTmG |
Knock-in | Described above | negative | [123, 124] |
R26R: Rosa26 reporter.
tTA: tetracycline transactivator.
TRE: tetracycline response element.
SVF: stromal vascular fraction.