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Cell competition during reprogramming gives rise to dominant clones
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Journal Article
Cell competition during reprogramming gives rise to dominant clones
2019
Overview
A Nobel Prize–winning discovery showed that specialized cells can be genetically reprogrammed into stem cells, thus gaining the ability to become any cell type in the body. But what happens during reprogramming is not completely understood. Shakiba et al. used experimental and mathematical approaches to show that skin cells compete during reprogramming, eliminating one another as the population progresses toward the stem cell state (see the Perspective by Wolff and Purvis). The “winners” are a special class of skin cells originating from the neural crest. Cells of this type normally emerge during embryonic development and migrate into various tissues, including the skin, muscle, and nervous system. Science , this issue p. eaan0925 ; see also p. 330 During reprogramming, specific cells display “eliteness” and emerge to dominate the reprogramming niche. 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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science,American Association for the Advancement of Science (AAAS)
