Format

Send to

Choose Destination
Science. 2019 Apr 26;364(6438). pii: eaan0925. doi: 10.1126/science.aan0925. Epub 2019 Mar 21.

Cell competition during reprogramming gives rise to dominant clones.

Author information

1
Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario M5S 3E1, Canada.
2
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
3
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
4
Department of Physics, University of Toronto, Toronto, Ontario M5S 1A7, Canada.
5
SFR-SANTE, iPSC Core Facility, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
6
CRTI, INSERM, Université de Nantes, Nantes, France.
7
ITUN, CHU Nantes, Nantes, France.
8
Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5T 3H7, Canada.
9
Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario M5G 1E2, Canada.
10
Institute of Medical Science, University of Toronto, Toronto, Ontario M5T 3H7, Canada.
11
Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia.
12
The Donnelly Centre for Cellular and Biomolecular Research (CCBR), University of Toronto, Toronto, Ontario M5S 3E1, Canada.
13
Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario M5S 3E1, Canada. peter.zandstra@ubc.ca.
14
School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
15
The Biomedical Research Centre, The University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
16
Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia V6T 1Z4, 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.

Comment in

PMID:
30898844
DOI:
10.1126/science.aan0925

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center