GEO series
Nodal/Smad2 signaling sustains developmental pausing by repressing Pparg -mediated lipid metabolism [ATAC-seq]
GSE302996
Mus musculus
Genome binding/occupancy profiling by high throughput sequencing
24 samples
Submitted 2026/06/22
Platform GPL34328
Summary
Cells and organisms can enter transient dormant states to survive unfavorable conditions during development, physiological adult states and disease. One paradigmatic case of dormancy is diapause, whereby embryos transiently pause development and enter a state of suspended animation. In mammals, diapause occurs pre-implantation at the blastocyst state and involves global growth suppression and metabolic rewiring towards lipid usage as energy source. The molecular regulation of diapause remains poorly understood, including whether it occurs by default or requires active signaling. Here, we identify the canonical TGF-β signaling pathway as an essential driver of transcriptional and metabolic reprogramming in diapause. TGF-β signaling was thought to only be required post-implantation, but we show that the ligand Nodal and its downstream effector Smad2 are essential for the survival of paused embryonic stem cells (ESCs) and blastocysts. Mechanistically, we found that Smad2 represses a Pparg, a transcription factor that is a master regulator of lipid storage, a process incompatible with pausing. Ablation of Pparg in Smad2-deficient ESCs rescues their survival and prevents excess lipid buildup in pausing conditions. These findings establish Nodal/Smad2 signaling as pivotal for sustaining embryonic diapause and suggest that the crosstalk between TGF-β signaling and the Pparg pathway may be broadly relevant for metabolic rewiring in dormancy contexts.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE302996_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 24 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1293325 and SRA study SRP601770. Searching any of these in the dataset finder brings you back here.
Study design
6 conditions, mostly with about 4 replicates each
ATAC, Ctrl, WT, ×4
ATAC, Ctrl, Smad2_KO1, ×4
ATAC, Ctrl, Smad2_KO2, ×4
ATAC, Paused, WT, ×4
ATAC, Paused, Smad2_KO1, ×4
ATAC, Paused, Smad2_KO2, ×4
Supports a between-group comparison across 24 samples.
6 replicated groups read from 24 sample titles; they account for 24 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9115326 ATAC, Ctrl, WT, rep 1
- GSM9115327 ATAC, Ctrl, WT, rep 2
- GSM9115328 ATAC, Ctrl, WT, rep 3
- GSM9115329 ATAC, Ctrl, WT, rep 4
- GSM9115330 ATAC, Ctrl, Smad2_KO1, rep 1
- GSM9115331 ATAC, Ctrl, Smad2_KO1, rep 2
- GSM9115332 ATAC, Ctrl, Smad2_KO1, rep 3
- GSM9115333 ATAC, Ctrl, Smad2_KO1, rep 4
- GSM9115334 ATAC, Ctrl, Smad2_KO2, rep 1
- GSM9115335 ATAC, Ctrl, Smad2_KO2, rep 2
- GSM9115336 ATAC, Ctrl, Smad2_KO2, rep 3
- GSM9115337 ATAC, Ctrl, Smad2_KO2, rep 4
- GSM9115338 ATAC, Paused, WT, rep 1
- GSM9115339 ATAC, Paused, WT, rep 2
- GSM9115340 ATAC, Paused, WT, rep 3
- GSM9115341 ATAC, Paused, WT, rep 4
- GSM9115342 ATAC, Paused, Smad2_KO1, rep 1
- GSM9115343 ATAC, Paused, Smad2_KO1, rep 2
- GSM9115344 ATAC, Paused, Smad2_KO1, rep 3
- GSM9115345 ATAC, Paused, Smad2_KO1, rep 4
- GSM9115346 ATAC, Paused, Smad2_KO2, rep 1
- GSM9115347 ATAC, Paused, Smad2_KO2, rep 2
- GSM9115348 ATAC, Paused, Smad2_KO2, rep 3
- GSM9115349 ATAC, Paused, Smad2_KO2, rep 4
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