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Stochastic promoter activation affects Nanog expression variability in mouse embryonic stem cells
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Stochastic promoter activation affects Nanog expression variability in mouse embryonic stem cells
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Journal Article
Stochastic promoter activation affects Nanog expression variability in mouse embryonic stem cells
2014
Overview
Mouse embryonic stem cells (mESCs) are self-renewing and capable of differentiating into any of the three germ layers. An interesting feature of mESCs is the presence of cell-to-cell heterogeneity in gene expression that may be responsible for cell fate decisions. Nanog, a key transcription factor for pluripotency, displays heterogeneous expression in mESCs, via mechanisms that are not fully understood. To understand this variability, we quantitatively analyzed
Nanog
transcription and found that
Nanog
was both infrequently transcribed and transcribed in a pulsatile and stochastic manner. It is possible that such stochastic transcriptional activation could contribute to the heterogeneity observed in
Nanog
expression as “intrinsic noise.” To discriminate the effects of both intrinsic noise from other (extrinsic) noise on the expression variability of
Nanog
mRNA, we performed allele-specific single-molecule RNA fluorescent
in situ
hybridization in a reporter cell line and found that intrinsic noise contributed to approximately 45% of the total variability in
Nanog
expression. Furthermore, we found that
Nanog
mRNA and protein levels were well correlated in individual cells. These results suggest that stochastic promoter activation significantly affects the Nanog expression variability in mESCs.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14/32
/ 14/63
/ 42/100
/ 42/41
/ Animals
/ Embryonic Stem Cells - cytology
/ Embryonic Stem Cells - metabolism
/ Embryos
/ Fluorescence in situ hybridization
/ Homeodomain Proteins - genetics
/ Homeodomain Proteins - metabolism
/ Humanities and Social Sciences
/ In Situ Hybridization, Fluorescence
/ Mice
/ Noise
/ Science
