Stem Cells and Development, Department of Developmental and Stem Cell Biology, Institut Pasteur, 25 Rue du Dr. Roux, 75015 Paris, France; CNRS UMR 3738, Institut Pasteur, Paris 75015, France; CNRS UMR 3664, Nuclear Dynamics, Institut Curie, Pavillon Pasteur, 26 Rue d'Ulm, 75005 Paris, France.
Stem Cells and Development, Department of Developmental and Stem Cell Biology, Institut Pasteur, 25 Rue du Dr. Roux, 75015 Paris, France; CNRS UMR 3738, Institut Pasteur, Paris 75015, France.
Cell Rep. 2020 Mar 10;30(10):3195-3206.e7. doi: 10.1016/j.celrep.2020.01.097.
Stem cells can be maintained through symmetric cell divisions (SCDs) and asymmetric cell divisions (ACDs). How and when these divisions occur in vivo in vertebrates is poorly understood. Here, we developed a clonogenic cell tracing method that demonstrates the asymmetric distribution of transcription factors along with old and new DNA in mouse muscle stem cells during skeletal muscle regeneration. Combining single-cell tracking and artificial niches ex vivo, we show how cells switch from ACDs to SCDs, suggesting that they are not engaged in an obligate mode of cell division. Further, we generated SNAP-tagged histone H3-reporter mice and find that, unlike fly germline stem cells, differential fate outcomes are associated with a symmetric distribution of the H3.1 and H3.3 histone variants in mouse muscle stem cells. This versatile and efficient H3-SNAP labeling system will allow an investigation of mechanisms underlying the maintenance of epigenomic identity and plasticity in a variety of tissues.
干细胞可以通过对称细胞分裂（SCDs）和不对称细胞分裂（ACDs）来维持。在脊椎动物中，这些分裂是如何以及何时在体内发生的，目前还了解甚少。在这里，我们开发了一种克隆形成细胞示踪方法，该方法证明了转录因子在骨骼肌肉再生过程中沿新旧 DNA 在小鼠肌肉干细胞中的不对称分布。通过单细胞跟踪和体外人工龛，我们展示了细胞如何从 ACD 转变为 SCD，这表明它们并非强制性地进行细胞分裂。此外，我们生成了 SNAP 标记的组蛋白 H3 报告小鼠，并发现与果蝇生殖干细胞不同，不同的命运结果与 H3.1 和 H3.3 组蛋白变体在小鼠肌肉干细胞中的对称分布有关。这种多功能且高效的 H3-SNAP 标记系统将允许研究维持各种组织中表观基因组身份和可塑性的机制。
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