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
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ISSN:1095-9203, 1095-9203
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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.
AbstractList 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.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.
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.
Author Wrana, Jeffrey L
Jayakumaran, Gowtham
Fahmy, Ahmed
David, Laurent
Elbaz, Judith
Goyal, Sidhartha
McGibbon, Sophie
Shakiba, Nika
Puri, Mira C
van der Kooy, Derek
Trcka, Daniel
Nagy, Andras
Zandstra, Peter W
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  orcidid: 0000-0003-0799-6122
  surname: Puri
  fullname: Puri, Mira C
  organization: Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5T 3H7, Canada
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  orcidid: 0000-0003-4311-0413
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  organization: Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia
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  surname: van der Kooy
  fullname: van der Kooy, Derek
  organization: The Donnelly Centre for Cellular and Biomolecular Research (CCBR), University of Toronto, Toronto, Ontario M5S 3E1, Canada
– sequence: 11
  givenname: Sidhartha
  surname: Goyal
  fullname: Goyal, Sidhartha
  organization: Department of Physics, University of Toronto, Toronto, Ontario M5S 1A7, Canada
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  surname: Zandstra
  fullname: Zandstra, Peter W
  email: peter.zandstra@ubc.ca
  organization: Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada
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References 30940927 - Nat Rev Genet. 2019 Jun;20(6):321
31023911 - Science. 2019 Apr 26;364(6438):330-331
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Snippet The ability to generate induced pluripotent stem cells from differentiated cell types has enabled researchers to engineer cell states. Although studies have...
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SubjectTerms 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
Title Cell competition during reprogramming gives rise to dominant clones
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