單細胞事業(yè)部 ｜ 歐易生物 V22.5 50
46
2021 年 IF：11.492
Abstract
Background: The heterogeneity of mesenchymal stem cells (MSCs) is poorly understood, thus limiting clinical
application and basic research reproducibility. Advanced single-cell RNA sequencing (scRNA-seq) is a robust tool used
to anal- yse for dissecting cellular heterogeneity. However, the comprehensive single-cell atlas for human MSCs has not
been achieved.
Methods: This study used massive parallel multiplexing scRNA-seq to construct an atlas of > 130 000 single-MSC
transcriptomes across multiple tissues and donors to assess their heterogeneity. The most widely clinically utilised tissue
resources for MSCs were collected, including normal bone marrow (n = 3), adi- pose (n = 3), umbilical cord (n = 2), and
dermis (n = 3).
Results: Seven tissue-specific and five conserved MSC subpopulations with distinct gene-expression signatures were
identified from multiple tissue ori- gins based on the high-quality data, which has not been achieved previously. This study
showed that extracellular matrix (ECM) highly contributes to MSC heterogeneity. Notably, tissue-specific MSC
subpopulations were sub- stantially heterogeneous on ECM-associated immune regulation, antigen
processing/presentation, and senescence, thus promoting inter-donor and intra-tissue heterogeneity. The variable dynamics
of ECM-associated genes had discrete trajectory patterns across multiple tissues. Additionally, the conserved and tissuespecific transcriptomic-regulons and protein-protein interactions were identified, potentially representing common or
tissue-specific MSC func- tional roles. Furthermore, the umbilical-cord-specific subpopulation possessed advantages in
immunosuppressive properties.
