Cell competition during reprogramming gives rise to dominant clones

Nika Shakiba 1 Ahmed Fahmy 2 Gowtham Jayakumaran 2, 3 Sophie Mcgibbon 4 Laurent David 5, 6, 7 Daniel Trcka 3 Judith Elbaz 3 Mira Puri 3, 8 Andras Nagy 3, 9, 10, 11 Derek van der Kooy 2, 12 Sidhartha Goyal 1, 4 Jeffrey Wrana 2, 3 Peter Zandstra 1, 12, 13, 14, 15, *
* Corresponding author
1 IBBME - Institute of Biomaterials and Biomedical Engineering [Ontario, Canada]
2 Department of Molecular Genetics [Toronto]
3 Mount Sinai Hospital - Lunenfeld-Tanenbaum Research Institute [Toronto, ON, Canada]
4 Department of Physics [Toronto]
5 P2R - INSERM UMS016/CNRS UMS3556/UN FED4203 - Plateforme "Production de protéines recombinantes"
SFR François Bonamy - Structure fédérative de recherche François Bonamy
6 ITUN - Institut de transplantation urologie-néphrologie
7 Team 2 - U1064 Inserm - CRTI - Genetic and Cellular Engineering in Immunology and Regenerative Medicine
U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
8 MBP - Department of Medical Biophysics
9 Department of Obstetrics and Gynecology [Toronto, ON, Canada]
10 Institute of Medical Science [Toronto]
11 Australian Regenerative Medicine Institute [Melbourne, Australia]
12 CCBR - The Donnelly Centre for Cellular and Biomolecular Research [Toronto, ON, Canada]
13 School of Biomedical Engineering [Vancouver, Canada]
14 The Biomedical Research Centre [Vancouver, Canada]
15 Michael Smith Laboratories [Vancouver, Canada]
Abstract : 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.
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Nika Shakiba, Ahmed Fahmy, Gowtham Jayakumaran, Sophie Mcgibbon, Laurent David, et al.. Cell competition during reprogramming gives rise to dominant clones. Science, American Association for the Advancement of Science, 2019, 364 (6438), Epub 2019 Mar 21. ⟨10.1126/science.aan0925⟩. ⟨inserm-02145973⟩

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