Transcriptome analyses of reprogrammed feather / scale chimeric explants revealed co-expressed epithelial gene networks during organ specification

Abstract

BackgroundThe molecular mechanism controlling regional specific skin appendage phenotypes is a fundamental question that remains unresolved. We recently identified feather and scale primordium associated genes and with functional studies, proposed five major modules are involved in scale-to-feather conversion and their integration is essential to form today’s feathers. Yet, how the molecular networks are wired and integrated at the genomic level is still unknown.ResultsHere, we combine classical recombination experiments and systems biology technology to explore the molecular mechanism controlling cell fate specification. In the chimeric explant, dermal fate is more stable, while epidermal fate is reprogrammed to be similar to the original appendage type of the mesenchyme. We analyze transcriptome changes in both scale-to-feather and feather-to-scale transition in the epidermis. We found a highly interconnected regulatory gene network controlling skin appendage types. These gene networks are organized around two molecular hubs, β-catenin and retinoic acid (RA), which can bind to regulatory elements controlling downstream gene expression, leading to scale or feather fates. ATAC sequencing analyses revealed about 1000 altered widely distributed chromatin open sites. We find that perturbation of a key gene alters the expression of many other co-expressed genes in the same module.ConclusionsOur findings suggest that these feather / scale fate specification genes form an interconnected network and rewiring of the gene network can lead to changes of appendage phenotypes, acting similarly to endogenous reprogramming at the tissue level. This work shows that key hub molecules, β-catenin and retinoic acid, regulate scale / feather fate specification gene networks, opening up new possibilities to understand the switches controlling organ phenotypes in a two component (epithelial and mesenchyme) system.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5184-x) contains supplementary material, which is available to authorized users.

Pigeon foot feathering reveals conserved limb identity networks

“…Spatiotemporal modulation of gene expression, particularly of genes like PITX1 and TBX5 that function at the top of gene regulatory hierarchies, is an important driver of evolutionary diversification (Davidson, 2006, Erwin and Davidson, 2009, Rebeiz et al, 2015. Generation of phenotypic diversity and novelty via co-option of genetic circuits or top-level network regulators is a repeated theme in evolution; notable examples include co-option of the adult skeletogenic network to form the larval skeleton in echinoderms, redeployment of the highly conserved arthropod appendage-patterning network to form beetle horns, and overlap of the genetic networks that control embryonic limb and external genital development in tetrapods (Rebeiz et al, 2015, Davidson, 2006, Erwin and Davidson, 2009, Infante et al, 2015, Gao and Davidson, 2008, Tschopp et al, 2014, Herrera and Cohn, 2014, Leal and Cohn, 2016. Our comparative analyses in pigeons indicate that TFs are a major component of the FL identity program redeployed in feathered HLs; similarly, others have noted that genes at the top of regulatory networks are more evolutionarily stable than differentiation genes at the network periphery (Davidson, 2006, Erwin and Davidson, 2009, Rebeiz et al, 2015.…”

Developmental plasticity of epithelial stem cells in tooth and taste bud renewal

“…Additionally, recent study demonstrates the conversion of characteristics between integument-derived epithelial appendages, including the growth of hair from teeth (21) and the transition from scales to feathers (22). In the latter case, transcriptome analyses implicated specific pathways, β-catenin and retinoic acid, in the process (23).…”

Chicken chromatin accessibility atlas accelerates epigenetic annotation of birds and gene fine-mapping associated with growth traits

“…A total of 53 ATAC-seq libraries derived from 11 tissue types (duodenum in this study and bone, bud, liver, lung, muscle, neural crest, retina, skin, somatopleure, and T cells from public datasets) ( Foissac et al, 2019 ; Halstead et al, 2020a ; Lai et al, 2018 ; Patoori et al, 2020 ; Rothstein & Simoes-Costa, 2020 ; Sackton et al, 2019 ; Young et al, 2019 ) were collected ( Table 1 ; Supplementary Table S1). Samples were analyzed for genome-wide chromatin accessibility using a standard pipeline (see details in the Materials and Methods) and passed through stringent quality filtering.…”

“…Each sample was quickly frozen in liquid nitrogen and stored at –80 °C until nuclear extraction. The sequencing data for other tissues were obtained from previous reports ( Foissac et al, 2019 ; Halstead et al, 2020a ; Lai et al, 2018 ; Patoori et al, 2020 ; Rothstein & Simoes-Costa, 2020 ; Sackton et al, 2019 ; Young et al, 2019 ). All samples used in this study and their sources are listed in Supplementary Table S1.…”