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...

Full description

Saved in:
Bibliographic Details
Published in:Science (American Association for the Advancement of Science) Vol. 364; no. 6438
Main Authors: 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
Format: Journal Article
Language:English
Published: United States 26.04.2019
Subjects:
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
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1095-9203
1095-9203
DOI:10.1126/science.aan0925