Author response: Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury

Comprehensive Integration of Single-Cell Transcriptional Profiling Reveals the Heterogeneities of Non-cardiomyocytes in Healthy and Ischemic Hearts

“…It is very important to understand the mechanism by which these cells finely orchestrate these proinflammatory and proreparative processes during cardiac remodeling via ligand and receptor interactions. In line with a previous study (10), the crosstalk among all subpopulations revealed that myofibroblasts and ECs are the key cell types involved in cellular communication, highlighting their pivotal role in remodeling processes. Moreover, the integrin family (e.g., Itgb1, Itga1, and Itgav) was found to be the most profound protein family participating in cellular crosstalk in our analysis.…”

“…In line with the scRNA-seq results, we validated the existence of endothelial-like macrophages by costaining CD31 and CD68 using immunofluorescence technology ( Figure 3J). Additionally, by ordering the pseudotime cell trajectory, we described a continuous stage of macrophages starting from early infiltrating monocytes and M1 macrophages to late proreparative M2 macrophages ( Figure 3K), which is similar to what has been found in previous studies on single-cell analysis (10) or in vivo experiments (21). However, it was found that other macrophage subpopulations, such as MAC_TR, MAC_Fib, and MAC_Endo, are hard to merge into the trajectory of blood-derived macrophages, suggesting a divergent origin and transcriptional profile of these two cell types.…”

“…Cell-cell communication networks were assessed according to a previously published algorithm (10). Briefly, a collection of ligand-receptor pairs generated from the STRING database (11) were further analyzed only if they expressed at least 10% of the cells in a given cell population.…”

Tailoring Cardiac Synthetic Transcriptional Modulation Towards Precision Medicine

“…Other heart-disease oriented studies have focused on the cellular composition upon ischemic injury in the murine heart (42,49,50). SCS of the interstitial cell population showed comprehensive dynamics of cardiac stromal, vascular and immune cells of healthy and ischemic hearts.…”

Post-ischemic Myocardial Inflammatory Response: A Complex and Dynamic Process Susceptible to Immunomodulatory Therapies

“…Upregulated chemokines and cytokines cause extravasation of activated blood-derived cells into the infarcted area (Figure 2), which play an important role in regulating the reparative response and are possible targets for cardioprotective therapies (151). Single-cell RNA-sequencing following unreperfused MI of the non-cardiomyocyte fraction revealed over 30 cell subtype populations, which highlighted post-ischemic non-linear dynamics in myeloid and fibroblast lineages crucial for understanding of cardiac homeostasis, inflammation, fibrosis, repair, and regeneration (152).…”