Cell competition during reprogramming gives rise to dominant clones

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...

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Vydáno v:Science (American Association for the Advancement of Science) Ročník 364; číslo 6438
Hlavní autoři: Shakiba, Nika, Fahmy, Ahmed, Jayakumaran, Gowtham, McGibbon, Sophie, David, Laurent, Trcka, Daniel, Elbaz, Judith, Puri, Mira C, Nagy, Andras, van der Kooy, Derek, Goyal, Sidhartha, Wrana, Jeffrey L, Zandstra, Peter W
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 26.04.2019
Témata:
Animals
Cellular Reprogramming - genetics
Cellular Reprogramming - physiology
Cellular Reprogramming Techniques
Clonal Evolution
Clone Cells - cytology
DNA - genetics
Fibroblasts - cytology
Induced Pluripotent Stem Cells - cytology
Mice
Models, Theoretical
ISSN:1095-9203, 1095-9203
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Shrnutí: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.
Bibliografie:ObjectType-Article-1
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ISSN:1095-9203
1095-9203
DOI:10.1126/science.aan0925