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

Abstract Background The 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-t...

Full description

Bibliographic Details
Main Authors: Yung-Chih Lai, Ya-Chen Liang, Ting-Xin Jiang, Randall B. Widelitz, Ping Wu, Cheng-Ming Chuong
Format: Article
Language:English
Published: BMC 2018-10-01
Series:BMC Genomics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12864-018-5184-x
_version_ 1828397714532990976
author Yung-Chih Lai
Ya-Chen Liang
Ting-Xin Jiang
Randall B. Widelitz
Ping Wu
Cheng-Ming Chuong
author_facet Yung-Chih Lai
Ya-Chen Liang
Ting-Xin Jiang
Randall B. Widelitz
Ping Wu
Cheng-Ming Chuong
author_sort Yung-Chih Lai
collection DOAJ
description Abstract Background The 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. Results Here, 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. Conclusions Our 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.
first_indexed 2024-12-10T08:51:08Z
format Article
id doaj.art-e53c5343e983494ea249db0ad56668ea
institution Directory Open Access Journal
issn 1471-2164
language English
last_indexed 2024-12-10T08:51:08Z
publishDate 2018-10-01
publisher BMC
record_format Article
series BMC Genomics
spelling doaj.art-e53c5343e983494ea249db0ad56668ea2022-12-22T01:55:34ZengBMCBMC Genomics1471-21642018-10-0119111210.1186/s12864-018-5184-xTranscriptome analyses of reprogrammed feather / scale chimeric explants revealed co-expressed epithelial gene networks during organ specificationYung-Chih Lai0Ya-Chen Liang1Ting-Xin Jiang2Randall B. Widelitz3Ping Wu4Cheng-Ming Chuong5Integrative Stem Cell Center, China Medical University Hospital, China Medical UniversityIntegrative Stem Cell Center, China Medical University Hospital, China Medical UniversityDepartment of Pathology, Keck School of Medicine, University of Southern CaliforniaDepartment of Pathology, Keck School of Medicine, University of Southern CaliforniaDepartment of Pathology, Keck School of Medicine, University of Southern CaliforniaIntegrative Stem Cell Center, China Medical University Hospital, China Medical UniversityAbstract Background The 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. Results Here, 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. Conclusions Our 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.http://link.springer.com/article/10.1186/s12864-018-5184-xFeatherScalePtilopodyEvo-devoRegionalizationRecombination
spellingShingle Yung-Chih Lai
Ya-Chen Liang
Ting-Xin Jiang
Randall B. Widelitz
Ping Wu
Cheng-Ming Chuong
Transcriptome analyses of reprogrammed feather / scale chimeric explants revealed co-expressed epithelial gene networks during organ specification
BMC Genomics
Feather
Scale
Ptilopody
Evo-devo
Regionalization
Recombination
title Transcriptome analyses of reprogrammed feather / scale chimeric explants revealed co-expressed epithelial gene networks during organ specification
title_full Transcriptome analyses of reprogrammed feather / scale chimeric explants revealed co-expressed epithelial gene networks during organ specification
title_fullStr Transcriptome analyses of reprogrammed feather / scale chimeric explants revealed co-expressed epithelial gene networks during organ specification
title_full_unstemmed Transcriptome analyses of reprogrammed feather / scale chimeric explants revealed co-expressed epithelial gene networks during organ specification
title_short Transcriptome analyses of reprogrammed feather / scale chimeric explants revealed co-expressed epithelial gene networks during organ specification
title_sort transcriptome analyses of reprogrammed feather scale chimeric explants revealed co expressed epithelial gene networks during organ specification
topic Feather
Scale
Ptilopody
Evo-devo
Regionalization
Recombination
url http://link.springer.com/article/10.1186/s12864-018-5184-x
work_keys_str_mv AT yungchihlai transcriptomeanalysesofreprogrammedfeatherscalechimericexplantsrevealedcoexpressedepithelialgenenetworksduringorganspecification
AT yachenliang transcriptomeanalysesofreprogrammedfeatherscalechimericexplantsrevealedcoexpressedepithelialgenenetworksduringorganspecification
AT tingxinjiang transcriptomeanalysesofreprogrammedfeatherscalechimericexplantsrevealedcoexpressedepithelialgenenetworksduringorganspecification
AT randallbwidelitz transcriptomeanalysesofreprogrammedfeatherscalechimericexplantsrevealedcoexpressedepithelialgenenetworksduringorganspecification
AT pingwu transcriptomeanalysesofreprogrammedfeatherscalechimericexplantsrevealedcoexpressedepithelialgenenetworksduringorganspecification
AT chengmingchuong transcriptomeanalysesofreprogrammedfeatherscalechimericexplantsrevealedcoexpressedepithelialgenenetworksduringorganspecification