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Title: Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation

Abstract

Yan is an ETS-domain transcription factor responsible for maintaining Drosophila eye cells in a multipotent state. Yan is at the core of a regulatory network that determines the time and place in which cells transit from multipotency to one of several differentiated lineages. Using a fluorescent reporter for Yan expression, we observed a biphasic distribution of Yan in multipotent cells, with a rapid inductive phase and slow decay phase. Transitions to various differentiated states occurred over the course of this dynamic process, suggesting that Yan expression level does not strongly determine cell potential. Consistent with this conclusion, perturbing Yan expression by varying gene dosage had no effect on cell fate transitions. However, we observed that as cells transited to differentiation, Yan expression became highly heterogeneous and this heterogeneity was transient. Signals received via the EGF Receptor were necessary for the transience in Yan noise since genetic loss caused sustained noise. As a result, since these signals are essential for eye cells to differentiate, we suggest that dynamic heterogeneity of Yan is a necessary element of the transition process, and cell states are stabilized through noise reduction.

Authors:
 [1];  [1];  [1];  [1];  [2];  [2];  [2];  [1];  [1];  [1]
  1. Northwestern Univ., Evanston, IL (United States)
  2. Univ. of Chicago, Chicago, IL (United States)
Publication Date:
Research Org.:
Northwestern Univ., Evanston, IL (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
1234765
Alternate Identifier(s):
OSTI ID: 1234766; OSTI ID: 1257261
Grant/Contract Number:  
NA0002520
Resource Type:
Published Article
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 4; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Pelaez, Nicolas, Gavalda-Miralles, Arnau, Wang, Bao, Navarro, Heliodoro Tejedor, Gudjonson, Herman, Rebay, Ilaria, Dinner, Aaron R., Katsaggelos, Aggelos K., Amaral, Luís A. N., and Carthew, Richard W. Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation. United States: N. p., 2015. Web. doi:10.7554/eLife.08924.
Pelaez, Nicolas, Gavalda-Miralles, Arnau, Wang, Bao, Navarro, Heliodoro Tejedor, Gudjonson, Herman, Rebay, Ilaria, Dinner, Aaron R., Katsaggelos, Aggelos K., Amaral, Luís A. N., & Carthew, Richard W. Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation. United States. doi:10.7554/eLife.08924.
Pelaez, Nicolas, Gavalda-Miralles, Arnau, Wang, Bao, Navarro, Heliodoro Tejedor, Gudjonson, Herman, Rebay, Ilaria, Dinner, Aaron R., Katsaggelos, Aggelos K., Amaral, Luís A. N., and Carthew, Richard W. Thu . "Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation". United States. doi:10.7554/eLife.08924.
@article{osti_1234765,
title = {Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation},
author = {Pelaez, Nicolas and Gavalda-Miralles, Arnau and Wang, Bao and Navarro, Heliodoro Tejedor and Gudjonson, Herman and Rebay, Ilaria and Dinner, Aaron R. and Katsaggelos, Aggelos K. and Amaral, Luís A. N. and Carthew, Richard W.},
abstractNote = {Yan is an ETS-domain transcription factor responsible for maintaining Drosophila eye cells in a multipotent state. Yan is at the core of a regulatory network that determines the time and place in which cells transit from multipotency to one of several differentiated lineages. Using a fluorescent reporter for Yan expression, we observed a biphasic distribution of Yan in multipotent cells, with a rapid inductive phase and slow decay phase. Transitions to various differentiated states occurred over the course of this dynamic process, suggesting that Yan expression level does not strongly determine cell potential. Consistent with this conclusion, perturbing Yan expression by varying gene dosage had no effect on cell fate transitions. However, we observed that as cells transited to differentiation, Yan expression became highly heterogeneous and this heterogeneity was transient. Signals received via the EGF Receptor were necessary for the transience in Yan noise since genetic loss caused sustained noise. As a result, since these signals are essential for eye cells to differentiate, we suggest that dynamic heterogeneity of Yan is a necessary element of the transition process, and cell states are stabilized through noise reduction.},
doi = {10.7554/eLife.08924},
journal = {eLife},
number = ,
volume = 4,
place = {United States},
year = {2015},
month = {11}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.7554/eLife.08924

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Cited by: 5 works
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