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Series GSE155862 Query DataSets for GSE155862
Status Public on Aug 08, 2020
Title b-catenin Signaling Dynamics Regulate Cell Fate in Differentiating Neural Stem Cells
Organism Rattus norvegicus
Experiment type Expression profiling by high throughput sequencing
Summary Stem cells undergo differentiation in complex and dynamic environments wherein instructive signals fluctuate on various timescales. Thus, cells must be equipped to properly respond to the timing of signals, for example to distinguish sustained signaling from transient noise. However, how stem cells respond to dynamic variations in differentiation cues is not well characterized. Here, we use optogenetic activation of b-catenin signaling to probe the dynamic responses of differentiating adult neural stem cells (NSCs). We discover that while elevated, sustained b-catenin activation sequentially promotes proliferation and differentiation, transient b-catenin induces apoptosis. Genetic perturbations revealed that the neurogenic/apoptotic fate-switch was mediated through cell cycle regulation by Growth Arrest and DNA Damage 45 gamma (Gadd45g). Our results thus reveal a role for b-catenin dynamics in NSC fate decisions and may suggest a novel role for signal timing to minimize cell fate errors, analogous to kinetic proofreading of stem cell differentiation.
Overall design RNA profiles of adult rat neural stem cells subjected to Wnt/b-catenin stimulation over 3-5 days. Stimulation was achieved using either CHIR99021 (3 mM), Wnt 3a (100 ng/mL), or optogenetics (optoWnt). Stimulation was applied for one day and was subsequently withdrawn for days 2 and 3. Control conditions include cells that received no stimulation, or cells that received constant stimulation over 3-5 days.
Contributor(s) Rosenbloom AB, Tarczyński M, Lam N, Kane RS, Bugaj LJ, Schaffer DV
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Submission date Aug 07, 2020
Last update date Oct 23, 2020
Contact name Lukasz Bugaj
Organization name University of Pennsylvania
Department Bioengineering
Lab Bugaj Lab
Street address 390 Towne Building, 220 S. 33rd St
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
Platforms (1)
GPL14844 Illumina HiSeq 2000 (Rattus norvegicus)
Samples (20)
GSM4714719 wild-type untreated 0d
GSM4714720 wild-type untreated 3d ON
GSM4714721 wild-type untreated 5d ON
BioProject PRJNA655888
SRA SRP276643

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Supplementary file Size Download File type/resource
GSE155862_rawCounts.csv.gz 3.8 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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