さて、先日 Cell Reports でオンラインに出てきた論文。
Cell competition promotes phenotypically silent cardiomyocyte replacement in the mammalian heart. Cell Reports doi: 10.1016/j.celrep.2014.08.005.
Heterogeneous anabolic capacity in cell populations can trigger a phenomenon known as cell competition, through which less active cells are eliminated. Cell competition has been induced experimentally in stem/precursor cell populations in insects and mammals and takes place endogenously in early mouse embryonic cells. Here, we show that cell competition can be efficiently induced in mouse cardiomyocytes by mosaic overexpression of Myc during both gestation and adult life. The expansion of the Myc-overexpressing cardiomyocyte population is driven by the elimination of wild-type cardiomyocytes. Importantly, this cardiomyocyte replacement is phenotypically silent and does not affect heart anatomy or function. These results show that the capacity for cell competition in mammals is not restricted to stem cell populations and suggest that stimulated cell competition has potential as a cardiomyocyte-replacement strategy.
ここ最近、マウス生体内におけるcell competitionがearly embryoとthymusで報告されてきたが、今回はcardiomyocyteにおけるcell competitionの報告。基本的にはMyc overexpressing cellによってwild-type cellがoutcompeteされるというおなじみの話なのだが、発生期間中だけでなくpostnatalのadult cardiomyocytesでもcompetitionによるreplacementが起こることが示されている。adult heartでのcompetitionを確認するために、モザイク導入後の経過を一年も見たりして頑張ってますなぁ。一つオモロイのは、developing heartではloserのwild-type cellはapoptosisを起こすのに対して、adult heartではapoptosisではなくautophagic cell deathによって除去されている点か。これについては、「Dying cells are normally eliminated by macrophages, but the size of an adult cardiomyocyte is about 100 times that of a macrophage, so a phase of self-destructive autophagy might be necessary before they can be eliminated by macrophages in a controlled manner.」とディスカスしている。なるへそ。あと、心臓ではCCHが起こるんかなぁと思っていたけど、意外とadult cardiomyocytesでもwinnerはcompensatory proliferationでreplaceしてるみたい。
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