PUBLICATION
leptin b and its regeneration enhancer illustrate the regenerative features of zebrafish hearts
- Authors
- Shin, K., Begeman, I.J., Cao, J., Kang, J.
- ID
- ZDB-PUB-221211-1
- Date
- 2022
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 253(1): 91-106 (Journal)
- Registered Authors
- Cao, Jingli, Kang, Junsu
- Keywords
- enhancer, heart, injury, leptin, regeneration, zebrafish
- MeSH Terms
-
- Animals
- Endocardium
- Heart
- Leptin/metabolism
- Myocytes, Cardiac*/metabolism
- Pericardium
- Zebrafish*/genetics
- PubMed
- 36495292 Full text @ Dev. Dyn.
Citation
Shin, K., Begeman, I.J., Cao, J., Kang, J. (2022) leptin b and its regeneration enhancer illustrate the regenerative features of zebrafish hearts. Developmental Dynamics : an official publication of the American Association of Anatomists. 253(1):91-106.
Abstract
Background Zebrafish possess a remarkable regenerative capacity, which is mediated by the induction of various genes upon injury. Injury-dependent transcription is governed by the tissue regeneration enhancer elements (TREEs). Here, we utilized leptin b (lepb), an injury-specific factor, and its TREE to dissect heterogeneity of non-cardiomyocytes (CMs) in regenerating hearts.
Results Our single-cell RNA sequencing (scRNA-seq) analysis demonstrated that the endothelium/endocardium(EC) is activated to induce distinct subpopulations upon injury. We demonstrated that lepb can be utilized as a regeneration-specific marker to subset injury-activated ECs. lepb+ ECs robustly induce pro-regenerative factors, implicating lepb+ ECs as a signaling center to interact with other cardiac cells. Our scRNA-seq analysis identified that lepb is also produced by subpopulation of epicardium (Epi) and epicardium-derived cells (EPDCs). To determine whether lepb labels injury-emerging non-CM cells, we tested the activity of lepb-linked regeneration enhancer (LEN) with chromatin accessibility profiles and transgenic lines. While non-detectable in uninjured hearts, LEN directs EC and Epi/EPDC expression upon injury. The endogenous LEN activity was assessed using LEN deletion lines, demonstrating that LEN deletion abolished injury-dependent expression of lepb, but not other nearby genes.
Conclusions Our integrative analyses identify regeneration-emerging cell-types and factors, leading to the discovery of regenerative features of hearts. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping