TY - JOUR
T1 - Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation
AU - Peláez, Nicolás
AU - Gavalda-Miralles, Arnau
AU - Wang, Bao
AU - Navarro, Heliodoro Tejedor
AU - Gudjonson, Herman
AU - Rebay, Ilaria
AU - Dinner, Aaron R.
AU - Katsaggelos, Aggelos K.
AU - Amaral, Luís A.N.
AU - Carthew, Richard W.
N1 - Publisher Copyright:
© Peláez et al.
PY - 2015/11/19
Y1 - 2015/11/19
N2 - 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.
AB - 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.
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U2 - 10.7554/eLife.08924
DO - 10.7554/eLife.08924
M3 - Article
C2 - 26583752
AN - SCOPUS:84955256177
SN - 2050-084X
VL - 4
JO - eLife
JF - eLife
IS - NOVEMBER2015
M1 - e08924
ER -