PUBLICATION

Single-cell chromatin profiling reveals genetic programs activating proregenerative states in nonmyocyte cells

Authors
Dong, Y., Yang, Y., Wang, H., Feng, D., Nist, E., Yapundich, N., Spurlock, B., Craft, M., Qian, L., Liu, J.
ID
ZDB-PUB-240222-18
Date
2024
Source
Science advances   10: eadk4694eadk4694 (Journal)
Registered Authors
Liu, Jiandong
Keywords
none
Datasets
GEO:GSE215987, GEO:GSE215986, GEO:GSE248538, GEO:GSE215988
MeSH Terms
  • Animals
  • Chromatin*/genetics
  • Gene Expression Regulation, Developmental
  • Heart/physiology
  • Regeneration/genetics
  • Zebrafish*/genetics
PubMed
38381829 Full text @ Sci Adv
Abstract
Cardiac regeneration requires coordinated participation of multiple cell types whereby their communications result in transient activation of proregenerative cell states. Although the molecular characteristics and lineage origins of these activated cell states and their contribution to cardiac regeneration have been studied, the extracellular signaling and the intrinsic genetic program underlying the activation of the transient functional cell states remain largely unexplored. In this study, we delineated the chromatin landscapes of the noncardiomyocytes (nonCMs) of the regenerating heart at the single-cell level and inferred the cis-regulatory architectures and trans-acting factors that control cell type-specific gene expression programs. Moreover, further motif analysis and cell-specific genetic manipulations suggest that the macrophage-derived inflammatory signal tumor necrosis factor-α, acting via its downstream transcription factor complex activator protein-1, functions cooperatively with discrete transcription regulators to activate respective nonCM cell types critical for cardiac regeneration. Thus, our study defines the regulatory architectures and intercellular communication principles in zebrafish heart regeneration.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping