Unveiling distinctions between mesenchymal stromal cells and stem cells by single-cell transcriptomic analysis

Mesenchymal stromal cells (MSCs) and stem cells are distinct types of cells, but they are practically undistinguishable by currently commonly-used identification markers. A single-cell transcriptomic analysis was used to solve this problem. There are eight critical genes involved in self-renewal and differentiation, <i>SOX2, NANOG, POU5F1, SFRP2, DPPA4, SALL4, ZFP42</i> and <i>MYCN</i> expressed in ESCs, iPSCs and adult stem cells (ASCs), but not in MSCs. There are five functional genes of MSCs, <i>TMEM119</i>, <i>FBLN5</i>, <i>KCNK2</i>, <i>CLDN11</i> and <i>DKK1</i>, which are not expressed in stem cells. Trajectory analysis displayed clear developmental cliffs from ESCs/iPSCs to ASCs and to MSCs. Adipose-derived MSCs, relative to other types of MSCs, exhibit a more consistent and broader spectrum of gene expression for regulatory and excrete function. This study identifies distinction markers between MSCs and stem cells, providing an alternative approach for quality control of MSCs in their propagation and further mechanistic insights into their action.