Artemov, A. | bioRxiv Science

bioRxiv2022

Epigenetic variations are landmarks of freshwater adaptation in threespine sticklebacks

For evolutionary biology, the phenotypic consequences of epigenetic variations and their potential contribution to adaptation and diversification are pressing issues. Marine and freshwater sticklebacks represent an ideal model for studying both genetic and epigenetic components of phenotypic plasticity that allow fish to inhabit water with different salinity. Here, we applied single-cell genomics (scRNA-seq and scATAC-seq) and whole-genome bisulfite sequencing to characterize intercellular variability in transcription, the abundance of open chromatin regions, and CpG methylation level in gills of marine and freshwater stickleback morphs. We found little difference in overall transcriptional variance between the morphs but observed significant changes in chromatin openness variance. In addition, genomic divergence islands (DIs) coincided with regions of increased methylation entropy in freshwater fish. Moreover, analysis of transcription factor binding sites within DIs revealed that [C]TCF motifs around marker SNPs were significantly enriched within the region. Altogether, our data show that increased epigenetic variance accompanies the adaptation of marine sticklebacks to freshwater.

evolutionary biology↗

bioRxiv2022

A branching model of cell fate decisions in the enteric nervous system

How neurogenesis and gliogenesis are coordinated during development and why mature glial cells often share properties with neuroectodermal progenitors remains unclear. Here, we have used single cell RNA sequencing to map the regulatory landscape of neuronal and glial differentiation in the mammalian enteric nervous system (ENS). Our analysis indicates that neurogenic trajectories branch directly from a linear gliogenic axis defined by autonomic neural crest cells adopting sequential states as they progressively lose their strong neurogenic bias and acquire properties of adult enteric glia. We identify gene modules associated with transcriptional programs driving enteric neurogenesis and cell state transitions along the gliogenic axis. By comparing the chromatin accessibility profile of autonomic neural crest and adult enteric glia we provide evidence that the latter maintain an epigenetic memory of their neurogenic past. Finally, we demonstrate that adult enteric glia maintain neurogenic potential and are capable of generating enteric neurons in certain contexts by activating transcriptional programs employed by early ENS progenitors. Our studies uncover a novel configuration of enteric neurogenesis and gliogenesis that enables the coordinate development of ENS lineages and provides a mechanistic explanation for the ability of enteric glia to be functionally integrated into the adult intestine and simultaneously maintain attributes of early ENS progenitors.

neuroscience↗