Single-cell transcriptomics following ischemic injury identifies a role for B2M in cardiac repair

TY - JOUR

T1 - Single-cell transcriptomics following ischemic injury identifies a role for B2M in cardiac repair

AU - Molenaar, Bas

AU - Timmer, Louk T

AU - Droog, Marjolein

AU - Perini, Ilaria

AU - Versteeg, Danielle

AU - Kooijman, Lieneke

AU - Monshouwer-Kloots, Jantine

AU - de Ruiter, Hesther

AU - Gladka, Monika M

AU - van Rooij, Eva

PY - 2021/1/29

Y1 - 2021/1/29

N2 - The efficiency of the repair process following ischemic cardiac injury is a crucial determinant for the progression into heart failure and is controlled by both intra- and intercellular signaling within the heart. An enhanced understanding of this complex interplay will enable better exploitation of these mechanisms for therapeutic use. We used single-cell transcriptomics to collect gene expression data of all main cardiac cell types at different time-points after ischemic injury. These data unveiled cellular and transcriptional heterogeneity and changes in cellular function during cardiac remodeling. Furthermore, we established potential intercellular communication networks after ischemic injury. Follow up experiments confirmed that cardiomyocytes express and secrete elevated levels of beta-2 microglobulin in response to ischemic damage, which can activate fibroblasts in a paracrine manner. Collectively, our data indicate phase-specific changes in cellular heterogeneity during different stages of cardiac remodeling and allow for the identification of therapeutic targets relevant for cardiac repair.

AB - The efficiency of the repair process following ischemic cardiac injury is a crucial determinant for the progression into heart failure and is controlled by both intra- and intercellular signaling within the heart. An enhanced understanding of this complex interplay will enable better exploitation of these mechanisms for therapeutic use. We used single-cell transcriptomics to collect gene expression data of all main cardiac cell types at different time-points after ischemic injury. These data unveiled cellular and transcriptional heterogeneity and changes in cellular function during cardiac remodeling. Furthermore, we established potential intercellular communication networks after ischemic injury. Follow up experiments confirmed that cardiomyocytes express and secrete elevated levels of beta-2 microglobulin in response to ischemic damage, which can activate fibroblasts in a paracrine manner. Collectively, our data indicate phase-specific changes in cellular heterogeneity during different stages of cardiac remodeling and allow for the identification of therapeutic targets relevant for cardiac repair.

KW - Animals

KW - Cell Line

KW - Disease Models, Animal

KW - Fibroblasts/metabolism

KW - Gene Expression Profiling

KW - Induced Pluripotent Stem Cells/metabolism

KW - Macrophages/metabolism

KW - Mice, Inbred C57BL

KW - Myocardial Reperfusion Injury/genetics

KW - Myocytes, Cardiac/metabolism

KW - Paracrine Communication

KW - Single-Cell Analysis

KW - Time Factors

KW - Transcriptome

KW - Ventricular Remodeling

KW - Wound Healing

KW - beta 2-Microglobulin/genetics

U2 - 10.1038/s42003-020-01636-3

DO - 10.1038/s42003-020-01636-3

M3 - Article

C2 - 33514846

SN - 2399-3642

VL - 4

SP - 146

JO - Communications Biology

JF - Communications Biology

IS - 1

ER -