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Preprint: Gene module reconstruction elucidates cellular differentiation processes and the regulatory logic of specialized secretion

December 29, 2023

New preprint!

We integrated gene expression dynamics from single-cell RNAseq developmental trajectories with functional annotations to generate gene modules that describe differentiation. When applied to the zebrafish axial mesoderm, these revealed known and newly associated differentiation processes (as well as their temporal ordering), including the anticipatory deployment of the unfolded protein response (UPR) in notochord and hatching gland differentiation. By profiling loss- and gain-of-function embryos, we found that the UPR transcription factors creb3l1, creb3l2, and xbp1 are master regulators of a general secretion program. creb3l1/creb3l2 additionally activate an extracellular matrix secretion program, while Xbp1 partners with Bhlha15 to activate a gland-specific secretion program. This reveals how the regulatory logic by which these related cell types activate shared and cell-type-specific secretory programs.

Read it at bioRxiv! external link

Phenotypes of UPR TF knockouts in the axial mesoderm

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