GSE117837
Transcriptional single cell analysis of human umbilical cord derived mesenchymal stem cells
Mesenchymal stem cells (MSCs) are a population of multipotent cells with an attractive ability to promote tissue repair by regulating regeneration and inflammation. Ironically, the immune regulatory capacity of MSCs, regardless of their tissue origin, is endowed by inflammatory cytokines (e.g., IFNg plus TNFa). Effective application of MSCs relies on the production of relatively homogeneous MSCs. However, the cellular heterogeneity, and the differentiation trajectories of in vitro expanded MSCs remains unclear. We profiled the transcriptomes of 361 single MSCs derived from two umbilical cords (UC-MSCs). The MSCs are from different passages and culture conditions with or without inflammatory cytokine stimulation. Weighted gene correlation network analysis for the expression of their highly variable genes revealed that UC-MSCs surprisingly possess only limited heterogeneity. Cell cycle based principal component analysis showed that the limited heterogeneity identified in these UC-MSCs was strongly associated with their entrance into the G2/M phase. This was further proven by the observation that one featured gene CD168 was expressed in a cell-cycle dependent manner. When CD168high UC-MSCs were sorted and cultured in vitro, they repopulated into a new community that is similar to the original status. Our results demonstrated that in vitro expanded UC-MSCs is a well-organized population with limited heterogeneity dominated by cell cycle status. Thus, our studies argues that standardization of MSCs for disease treatment is possible. Overall design: MSCs isolation from the umbilical cord, in vitro expansion, pretreatment approach, single cell capture, and RNA sequencing. Cells isolated from two different donors are sequenced in three passages with or without cytokine stimulation.Donor1, passage5, naive, 52cells; Donor2, passage5, naive, 50cells; Donor2, passage2, naive, 50cells; Donor2, passage0, naive, 50cells; Donor1, passage5, stimulation, 59cells; Donor2, passage5, stimulation, 50cells; Donor2, passage2, stimulation, 50cells;