My guess is that 70-80% (maybe higher) of RNA-seq experiments are with in vitro samples, as opposed to in vivo samples.
From what I've heard/read, it is very common for in vivo RNA-seq experiments with sample sizes of 5-20 per group to yield less than 20 (sometimes 0) differentially expressed genes after FDR-correction. In the field, it is common for papers doing experiments like this to use nominal p-values for this reason.
Now, when doing in vitro RNA-seq experiments, using sample sizes of 5-20 often does yield DEGs after FDR-correction. I wonder why this is. My two ideas are:
Standardization is much easier in vitro than in vivo, and this reduces variability and enables effects to reach statistical significance. The variability you find in vivo can often prevent FDR-corrected DEGs from being identified.
Experimental perturbations are more effective in vitro than in vivo. Cell cultures are more open systems that can more easily be perturbed than animals' bodies which are constantly fighting to reach homeostasis and resist experimental interventions.
Would love to know what you all think!