The heterogeneity of human umbilical cord mesenchymal stem cells (hUC-MSCs) is culturing-dependent, resulting in functional non-uniformness. To achieve the best clinical benefit, a comprehensive understanding of the origin of the heterogeneity in different culture systems can identify functional subgroups to direct the precise application of hUC-MSCs. Here, we create a single-cell transcriptome atlas of hUC-MSC in different culture systems for the identification of a subgroup of Ultroser-G-MSCs with high osteogenic and chondrogenic potentials featured by high expressions of IL1R1 and PDGFRA. Further experimental validations surprisingly reveal that IL1R1