Mesenchymal stromal cells in the bone marrow niche consist of multi-populations with distinct transcriptional and epigenetic properties [scRNA-Seq]

Although multiple studies have investigated the mesenchymal stem and progenitor cells (MSCs) that give rise to mature bone marrow, high heterogeneity in their morphologies and properties causes difficulties in molecular separation of their distinct populations. In this study, by taking advantage of the resolution of the single cell transcriptome, we analyzed Sca-1 and PDGFR-α fraction in the mouse bone marrow tissue. The single cell transcriptome enabled us to further classify the population into seven populations according to their gene expression profiles. We then separately obtained the seven populations based on candidate marker genes, and specified their gene expression properties and epigenetic landscape by ATAC-seq. Our findings will enable to elucidate the stem cell niche signal in the bone marrow microenvironment, reconstitute bone marrow in vitro, and shed light on the potentially important role of identified subpopulation in various clinical applications to the treatment of bone- and bone marrow-related diseases.

尽管已有多项研究针对可分化为成熟骨髓的间充质干细胞与祖细胞（mesenchymal stem and progenitor cells, MSCs）展开了探索，但这类细胞在形态与功能特性上存在高度异质性，使得难以通过分子手段分离其不同亚群。本研究借助单细胞转录组测序的分辨率，对小鼠骨髓组织中的Sca-1与PDGFRα阳性分群进行了分析。依托单细胞转录组数据，我们可根据基因表达谱将该细胞群进一步划分为7个亚群。随后我们通过候选标记基因分别分离得到这7个亚群，并利用ATAC-seq技术明确了各亚群的基因表达特性与表观遗传图谱。本研究结果有助于阐明骨髓微环境中的干细胞龛信号，实现骨髓的体外重构，并为明确所鉴定的细胞亚群在骨及骨髓相关疾病治疗的各类临床应用中的潜在重要作用提供了新的思路。