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. 2019 Sep 16;68(10):1874–1885. doi: 10.2337/db19-0308

Figure 1.

Figure 1

Evaluating the cellular origin of beige adipocytes through lineage tracing. A: Potential cellular origins of beige adipocytes. In principle, beige adipocytes (UCP1+ multilocular adipocytes) can arise through de novo differentiation of beige adipocyte precursors (i.e., adipogenesis) or through a cellular conversion in which existing mature adipocytes transform into beige cells. B: Genetic components of the AdipoChaser mouse model. AdipoChaser mice are a combination of three published transgenic lines: 1) transgenic mice expressing the gene encoding the “tet-on” transcription factor rtTA under the control of the adipoq gene promoter (“AdnP-rtTA”), 2) a tet-responsive CRE (TRE-Cre) line that can be activated by rtTA in the presence of doxycycline (Dox), and 3) Rosa26 reporter mice expressing membrane-bound GFP (mGFP) from the Rosa26 locus in a Cre-dependent manner (Rosa26-loxP-mtdTomato-loxP-mGFP). In the absence of doxycycline, all cells express membrane-bound tdTomato (mtdTomato). Upon treatment with doxycycline, rtTA activates the TRE promoter to induce Cre expression, and Cre protein will subsequently eliminate the floxed mtdTomato cassette and permanently turn on mGFP expression in every mature adiponectin-expressing adipocyte present during doxycycline exposure. C: Pulse-chase lineage tracing to reveal origins of beige adipocytes. Treatment of AdipoChaser mice with doxycycline (+ Dox) (via chow diet) for 10 days results in specific expression of mGFP in mature adipocytes (i.e., “pulse-labeling”). Upon removal of doxycycline (− Dox), animals are switched to cold temperatures or administered a thermogenic stimulus (e.g., β3-adrenergic receptor agonist) for a specified time period (i.e., “the Chase”). During this period there is no longer active Cre expression/adipocyte labeling. mGFP+ beige adipocytes appearing following the period of WAT “browning” represent beige adipocytes that arise from preexisting mature adipocytes. mGFP− beige adipocytes represent cells that arise de novo, presumably from resident adipocyte precursors.