Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Science. 2019 Apr 26;364(6438). doi: 10.1126/science.aan0925. Epub 2019 Mar 21.
The ability to generate induced pluripotent stem cells from differentiated cell types has enabled researchers to engineer cell states. Although studies have identified molecular networks that reprogram cells to pluripotency, the cellular dynamics of these processes remain poorly understood. Here, by combining cellular barcoding, mathematical modeling, and lineage tracing approaches, we demonstrate that reprogramming dynamics in heterogeneous populations are driven by dominant "elite" clones. Clones arise a priori from a population of poised mouse embryonic fibroblasts derived from Wnt1-expressing cells that may represent a neural crest-derived population. This work highlights the importance of cellular dynamics in fate programming outcomes and uncovers cell competition as a mechanism by which cells with eliteness emerge to occupy and dominate the reprogramming niche.
诱导多能干细胞（induced pluripotent stem cells，iPSCs）的生成能力使研究人员能够对细胞状态进行工程设计。尽管研究已经确定了将细胞重编程为多能性的分子网络，但这些过程的细胞动态仍知之甚少。在这里，我们通过结合细胞条形码、数学建模和谱系追踪方法，证明了异质群体中的重编程动力学是由主导的“精英”克隆驱动的。克隆预先从源自 Wnt1 表达细胞的、处于休眠状态的小鼠胚胎成纤维细胞（mouse embryonic fibroblasts，MEFs）群体中产生，这些细胞可能代表神经嵴衍生的群体。这项工作强调了细胞动态在命运编程结果中的重要性，并揭示了细胞竞争是具有精英性的细胞出现并占据和主导重编程生态位的机制。
