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. 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.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, United States.|Department of Chemical and Biological Engineering, Howard Hughes Medical Institute, University Northwestern, Evanston, United States.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Peláez
authors.affiliation: Department of Chemical and Biological Engineering, Howard Hughes Medical Institute, University Northwestern, Evanston, United States.
authors.forename: Arnau
authors.initials: A
authors.lastname: Gavalda-Miralles
authors.affiliation: Department Electrical Engineering and Computer Science, Northwestern University, Evanston, United States.
authors.forename: Bao
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Chemical and Biological Engineering, Howard Hughes Medical Institute, University Northwestern, Evanston, United States.
authors.forename: Heliodoro Tejedor
authors.initials: HT
authors.lastname: Navarro
authors.affiliation: James Franck Institute, University of Chicago, Chicago, United States.
authors.forename: Herman
authors.initials: H
authors.lastname: Gudjonson
authors.affiliation: Ben May Department for Cancer Research, University of Chicago, Chicago, United States.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Rebay
authors.affiliation: James Franck Institute, University of Chicago, Chicago, United States.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Dinner
authors.affiliation: Department Electrical Engineering and Computer Science, Northwestern University, Evanston, United States.
authors.forename: Aggelos K
authors.initials: AK
authors.lastname: Katsaggelos
authors.affiliation: Department of Chemical and Biological Engineering, Howard Hughes Medical Institute, University Northwestern, Evanston, United States.|Department of Physics and Astronomy, Northwestern University, Evanston, United States.
authors.forename: Luís A N
authors.initials: LA
authors.lastname: Amaral
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, United States.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Carthew
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D005123:Eye / Q000196:embryology; D005136:Eye Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: C076188:AOP protein, Drosophila; D029721:Drosophila Proteins; D005136:Eye Proteins; D012097:Repressor Proteins
keywords: D. melanogaster; EGF Receptor; computational biology; developmental biology; eye development; retinal cell differentiation; stem cells; systems biology