@article{75139aa428fd4d09858cc1798868a428,
title = "Cell-Type-Specific Gene Regulatory Networks Underlying Murine Neonatal Heart Regeneration at Single-Cell Resolution",
abstract = "The adult mammalian heart has limited capacity for regeneration following injury, whereas the neonatal heart can readily regenerate within a short period after birth. Neonatal heart regeneration is orchestrated by multiple cell types intrinsic to the heart, as well as immune cells that infiltrate the heart after injury. To elucidate the transcriptional responses of the different cellular components of the mouse heart following injury, we perform single-cell RNA sequencing on neonatal hearts at various time points following myocardial infarction and couple the results with bulk tissue RNA-sequencing data collected at the same time points. Concomitant single-cell ATAC sequencing exposes underlying dynamics of open chromatin landscapes and regenerative gene regulatory networks of diverse cardiac cell types and reveals extracellular mediators of cardiomyocyte proliferation, angiogenesis, and fibroblast activation. Together, our data provide a transcriptional basis for neonatal heart regeneration at single-cell resolution and suggest strategies for enhancing cardiac function after injury.",
keywords = "angiogenesis, cardiomyocyte proliferation, epicardial cells, fibrosis, injury response, myocardial infarction, open chromatin landscape, secreted factors, single cell ATAC-seq, single cell RNA-seq",
author = "Zhaoning Wang and Miao Cui and Shah, {Akansha M.} and Wei Tan and Ning Liu and Rhonda Bassel-Duby and Olson, {Eric N.}",
note = "Funding Information: We would like to thank Drs. Jian Xu, Yoon Jung Kim, and Xin Liu from the Next Generation Sequencing Core Facility at Children{\textquoteright}s Research Institute at the University of Texas Southwestern Medical Center for performing the Illumina sequencing. We thank Jose Cabrera for help with graphics; Stephen Johnson for help with high-performance computing; Drs. Ngoc Uyen Nhi Nguyen and Elisa Villalobos for technical advice on cardiac FB culture; Drs. Kedryn Baskin, Catherine Makarewich, and Hisayuki Hashimoto for advice on cardiac cell isolation; and Drs. Genevieve Konopka, Fatma Ayhan, and Marissa Co for help with setting up the single-cell workflow. We thank Dr. Len Pennacchio and the VISTA Enhancer Browser for the transgenic enhancer reporter analysis, and Dr. Huocong Huang for sharing reagents. We thank members of the Olson lab for discussions and Dr. Wenduo Ye for scientific inspiration. This work was supported by grants from the NIH ( AR-067294 , HL-130253 , HL-138426 , and HD-087351 ), the Fondation Leducq Transatlantic Networks of Excellence in Cardiovascular Research , and the Robert A. Welch Foundation ( 1-0025 to E.N.O.). Z.W. was supported by a predoctoral fellowship from the American Heart Association and the Harry S. Moss Heart Trust ( 19PRE34380436 ). Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = dec,
day = "8",
doi = "10.1016/j.celrep.2020.108472",
language = "English (US)",
volume = "33",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "10",
}