Genomics

Dataset Information

158

Temporal Layering of Signaling Effectors Drives Chromatin Remodeling during Hair Follicle Stem Cell Lineage Progression [ATAC-seq]


ABSTRACT: Tissue regeneration relies on resident stem cells (SCs), whose activity and lineage choices are influenced by microenvironment. Exploiting the synchronized, cyclical bouts of tissue regeneration in hair follicles (HFs), we investigate how microenvironment dynamics shape the emergence of SC lineages. Employing epigenetic and ChIP-seq profiling, we uncover how signal-dependent transcription factors couple spatio-temporal cues to chromatin dynamics, thereby choreographing SC lineages. Using enhancer-driven reporters, mutagenesis and genetics, we show that simultaneous BMP-inhibitory and WNT signals set the stage for lineage choices by establishing chromatin platforms permissive for diversification. Mechanistically, when binding of BMP-effector pSMAD1 is relieved, super-enhancers driving HF-SC master regulators become silenced. Concomitantly, multipotent, lineage-fated super-enhancers silent in HF-SCs become activated by exchanging WNT-effectors TCF3/4 for LEF1. Throughout regeneration, lineage super-enhancers continue reliance upon LEF1, but then achieve specificity by accommodating additional incoming signaling effectors. Barriers to progenitor plasticity mount as diverse, signal-sensitive transcription factors shape LEF1-regulated super-enhancer dynamics. Overall design: Mouse bulge hair follicle stem cell and hair germ cells at telogen stage and basal transient amplifying cells (TACs) and suprabasal TACs at anagen were FACS-purified and analyzed by ATAC-seq

INSTRUMENT(S): Illumina HiSeq 2000 (Mus musculus)

SUBMITTER: Hanseul Yang  

PROVIDER: GSE100875 | GEO | 2018-01-11

SECONDARY ACCESSION(S): PRJNA393328

REPOSITORIES: GEO

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Publications

Temporal Layering of Signaling Effectors Drives Chromatin Remodeling during Hair Follicle Stem Cell Lineage Progression.

Adam Rene C RC   Yang Hanseul H   Ge Yejing Y   Lien Wen-Hui WH   Wang Ping P   Zhao Yilin Y   Polak Lisa L   Levorse John J   Baksh Sanjeethan C SC   Zheng Deyou D   Fuchs Elaine E  

Cell stem cell 20180111 3


Tissue regeneration relies on resident stem cells (SCs), whose activity and lineage choices are influenced by the microenvironment. Exploiting the synchronized, cyclical bouts of tissue regeneration in hair follicles (HFs), we investigate how microenvironment dynamics shape the emergence of stem cell lineages. Employing epigenetic and ChIP-seq profiling, we uncover how signal-dependent transcription factors couple spatiotemporal cues to chromatin dynamics, thereby choreographing stem cell lineag  ...[more]

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