Altered Cohesin Dynamics During Cellular Differentiation

To test functional consequences, we generated homozygous degron alleles for Wapl and Esco1 and induced acute degradation using a dTAG-based system. Loss of WAPL altered cell-cycle dynamics in stem cells and produced a characteristic “vermicelli” chromosome phenotype, consistent with abnormally high and lethal cohesin retention on chromatin. Surprisingly, depletion of ESCO1 had no clear impact on viability and cell cycle progression.

Notably, despite loss of detectable WAPL protein in the differentiated cell population, induced WAPL degradation in these cells also resulted in the formation of vermicelli, indicating that the low level of WAPL remains functionally required. Together, these findings identify cohesin regulators, rather than cohesin abundance, as central drivers of changes in cohesin dynamics during differentiation. They further show that even very low levels of WAPL continue to provide critical structural plasticity of chromosomes following cell cycle exit and lineage commitment.