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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:
; ; ; ; ; ; ; ; ;
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 Name: eLife 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

Peláez, Nicolás, Gavalda-Miralles, Arnau, Wang, Bao, Navarro, Heliodoro Tejedor, Gudjonson, Herman, Rebay, Ilaria, Dinner, Aaron R., Katsaggelos, Aggelos K., Amaral, Luís AN, 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.
Peláez, Nicolás, Gavalda-Miralles, Arnau, Wang, Bao, Navarro, Heliodoro Tejedor, Gudjonson, Herman, Rebay, Ilaria, Dinner, Aaron R., Katsaggelos, Aggelos K., Amaral, Luís AN, & Carthew, Richard W. Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation. United States. doi:10.7554/eLife.08924.
Peláez, Nicolás, Gavalda-Miralles, Arnau, Wang, Bao, Navarro, Heliodoro Tejedor, Gudjonson, Herman, Rebay, Ilaria, Dinner, Aaron R., Katsaggelos, Aggelos K., Amaral, Luís AN, 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 = {Peláez, Nicolás 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 AN 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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Works referenced in this record:

Consecutive Positive Feedback Loops Create a Bistable Switch that Controls Preadipocyte-to-Adipocyte Conversion
journal, October 2012


Neuronal differentiation in the Drosophila ommatidium
journal, April 1987


Overlapping Activators and Repressors Delimit Transcriptional Response to Receptor Tyrosine Kinase Signals in the Drosophila Eye
journal, September 2000


Reciprocal inhibition between Pax7 and muscle regulatory factors modulates myogenic cell fate determination
journal, June 2007

  • Olguin, Hugo C.; Yang, Zhihong; Tapscott, Stephen J.
  • The Journal of Cell Biology, Vol. 177, Issue 5
  • DOI: 10.1083/jcb.200608122

Statistical Mechanics of Pluripotency
journal, August 2013


The regulation and functions of MAPK pathways in Drosophila
journal, June 2014


A comparative study of Pointed and Yan expression reveals new complexity to the transcriptional networks downstream of receptor tyrosine kinase signaling
journal, January 2014

  • Boisclair Lachance, Jean-François; Peláez, Nicolás; Cassidy, Justin J.
  • Developmental Biology, Vol. 385, Issue 2
  • DOI: 10.1016/j.ydbio.2013.11.002

Combinatorial Signaling in the Specification of Unique Cell Fates
journal, September 2000


Deconstructing transcriptional heterogeneity in pluripotent stem cells
journal, December 2014

  • Kumar, Roshan M.; Cahan, Patrick; Shalek, Alex K.
  • Nature, Vol. 516, Issue 7529
  • DOI: 10.1038/nature13920

Ras Pathway Specificity Is Determined by the Integration of Multiple Signal-Activated and Tissue-Restricted Transcription Factors
journal, September 2000


Evidence that Fold-Change, and Not Absolute Level, of β-Catenin Dictates Wnt Signaling
journal, December 2009


Development of the Drosophila retina, a neurocrystalline lattice
journal, October 1976


The Incoherent Feedforward Loop Can Provide Fold-Change Detection in Gene Regulation
journal, December 2009


atonal is the proneural gene for Drosophila photoreceptors
journal, June 1994

  • Jarman, Andrew P.; Grell, Ellsworth H.; Ackerman, Larry
  • Nature, Vol. 369, Issue 6479
  • DOI: 10.1038/369398a0

Gene expression heterogeneities in embryonic stem cell populations: origin and function
journal, December 2011

  • Martinez Arias, Alfonso; Brickman, Joshua M.
  • Current Opinion in Cell Biology, Vol. 23, Issue 6
  • DOI: 10.1016/j.ceb.2011.09.007

A Homeodomain Protein Code Specifies Progenitor Cell Identity and Neuronal Fate in the Ventral Neural Tube
journal, May 2000


Ligand-dependent activation of breathless FGF receptor gene in Drosophila developing trachea
journal, June 2002


Nkx6 Transcription Factors and Ptf1a Function as Antagonistic Lineage Determinants in Multipotent Pancreatic Progenitors
journal, June 2010


Signalling by the sevenless protein tyrosine kinase is mimicked by Rasl activation
journal, February 1992

  • Fortini, Mark E.; Simon, Michael A.; Rubin, Gerald M.
  • Nature, Vol. 355, Issue 6360
  • DOI: 10.1038/355559a0

A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways
journal, March 1994


Modeling bistable cell-fate choices in the Drosophila eye: qualitative and quantitative perspectives
journal, June 2010

  • Graham, T. G. W.; Tabei, S. M. A.; Dinner, A. R.
  • Development, Vol. 137, Issue 14
  • DOI: 10.1242/dev.044826

Homothorax Switches Function of Drosophila Photoreceptors from Color to Polarized Light Sensors
journal, October 2003


Positive Feedback Between PU.1 and the Cell Cycle Controls Myeloid Differentiation
journal, July 2013


Fractal dynamics in physiology: Alterations with disease and aging
journal, February 2002

  • Goldberger, A. L.; Amaral, L. A. N.; Hausdorff, J. M.
  • Proceedings of the National Academy of Sciences, Vol. 99, Issue Supplement 1
  • DOI: 10.1073/pnas.012579499

Ras1 signaling and transcriptional competence in the R7 cell of Drosophila.
journal, September 1996

  • Kauffmann, R. C.; Li, S.; Gallagher, P. A.
  • Genes & Development, Vol. 10, Issue 17
  • DOI: 10.1101/gad.10.17.2167

Threshold responses to morphogen gradients by zero‐order ultrasensitivity
journal, January 2005

  • Melen, Gustavo J.; Levy, Sagi; Barkai, Naama
  • Molecular Systems Biology, Vol. 1, Issue 1
  • DOI: 10.1038/msb4100036

Mutations affecting the pattern of the larval cuticle inDrosophila melanogaster: II. Zygotic loci on the third chromosome
journal, January 1984

  • J�rgens, G.; Wieschaus, E.; N�sslein-Volhard, C.
  • Wilhelm Roux's Archives of Developmental Biology, Vol. 193, Issue 5
  • DOI: 10.1007/BF00848157

Analysis of mutants in chaoptin, a photoreceptor cell-specific glycoprotein in Drosophila, reveals its role in cellular morphogenesis
journal, January 1988


Cell-type-specific transcription of prospero is controlled by combinatorial signaling in the Drosophila eye
journal, July 2008

  • Hayashi, T.; Xu, C.; Carthew, R. W.
  • Development, Vol. 135, Issue 16
  • DOI: 10.1242/dev.006189

Transcriptome-wide noise controls lineage choice in mammalian progenitor cells
journal, May 2008

  • Chang, Hannah H.; Hemberg, Martin; Barahona, Mauricio
  • Nature, Vol. 453, Issue 7194
  • DOI: 10.1038/nature06965

Characterization of the Drosophila segment determination morphome
journal, January 2008


A bistable Rb–E2F switch underlies the restriction point
journal, March 2008

  • Yao, Guang; Lee, Tae Jun; Mori, Seiichi
  • Nature Cell Biology, Vol. 10, Issue 4
  • DOI: 10.1038/ncb1711

Origins and implications of pluripotent stem cell variability and heterogeneity
journal, May 2013

  • Cahan, Patrick; Daley, George Q.
  • Nature Reviews Molecular Cell Biology, Vol. 14, Issue 6
  • DOI: 10.1038/nrm3584

Multilineage Transcriptional Priming and Determination of Alternate Hematopoietic Cell Fates
journal, August 2006


A MicroRNA Imparts Robustness against Environmental Fluctuation during Development
journal, April 2009


Dynamics of Dpp Signaling and Proliferation Control
journal, March 2011


Dynamics and Variability of ERK2 Response to EGF in Individual Living Cells
journal, December 2009


Hedgehog directly controls initiation and propagation of retinal differentiation in the Drosophila eye
journal, December 1997


Transcription factor heterogeneity in pluripotent stem cells: a stochastic advantage
journal, May 2014

  • Torres-Padilla, M. -E.; Chambers, I.
  • Development, Vol. 141, Issue 11
  • DOI: 10.1242/dev.102624

Cell clones and pattern formation: On the lineage of photoreceptor cells in the compound eye ofDrosophila
journal, January 1977

  • Campos-Ortega, J. A.; Hofbauer, A.
  • Wilhelm Roux's Archives of Developmental Biology, Vol. 181, Issue 3
  • DOI: 10.1007/BF00848423

Ommatidial development in Drosophila eye disc fragments
journal, October 1986