Single-cell transcriptomics uncover distinct innate and adaptive cell subsets during tissue homeostasis and regeneration

Abstract

Recently, immune cell-mediated tissue repair and regeneration has been an emerging paradigm of regenerative medicine. Immune cells form an essential part of the wound as induction of inflammation is a necessary step to elicit tissue healing. Rapid progress in transcriptomic analyses by high-throughput next-generation sequencing has been developed to study gene regulatory network and establish molecular signatures of immune cells that could potentially predict their functional roles in tissue repair and regeneration. However, the identification of cellular heterogeneity especially on the rare cell subsets has been limited in transcriptomic analyses of bulk cell populations. Therefore, genome-wide, single-cell RNA sequencing (scRNA-Seq) has offered an unprecedented approach to unravel cellular diversity and to study novel immune cell populations involved in tissue repair and regeneration through unsupervised sampling of individual cells without the need to rely on prior knowledge about cell-specific markers. The analysis of gene expression patterns at a single-cell resolution also holds promises to uncover the mechanisms and therefore the development of therapeutic strategy promoting immunoregenerative medicine. In this review, we will discuss how scRNA-Seq facilitates the characterization of immune cells, including macrophages, innate lymphoid cells and T and B lymphocytes, discovery of immune cell heterogeneity, identification of novel subsets, and tracking of developmental trajectories of distinct immune cells during tissue homeostasis, repair, and regeneration.

Macrophage Related Chronic Inflammation in Non-Healing Wounds

“…Another issue is scRNA-Seq deciphering at a transcriptome level, as it is difficult to examine the abundance and post-translation of proteins, or provide spatial information of individual cells. The integrative analysis of multiomics data, such as scRNA-seq, spatial transcriptomics, proteome, histology and epigenome, etc., is to build a three -dimensional localized microenvironment conducive to resolve this question ( 212 ). An additional problem is the integration principle, as the occurrence of chronic wounds is affected by both local and systemic factors.…”

What sequencing technologies can teach us about innate immunity*

“…While bulk sequencing provides a systems level view of gene regulation within a given population of cells it fails to describe the variety of responses between individual cells following activation. Single-cell RNA-seq (scRNA-seq) allows for the identification and classification of new cell types based on their gene expression profiles as well as providing insights into how cells within a population respond to a given stimulus[144][145][146] Shalek et al, produced two of the earliest single-cell studies examining the responses of bone marrow-derived dendritic cells (BMDCs) to…”