Adult stem and progenitor cells play fundamental roles in tissue renewal and regeneration. When these cells become dysfunctional, they contribute to a myriad of diseases including cancer, fibrosis and degenerative disorders. In the Underhill lab, we focus on a "universal" tissue-resident adult stem/progenitor cell termed a mesenchymal progenitor (MP). In response to tissue injury, MPs produce a microenvironment to support tissue regeneration (restoration of function) or repair (fibrosis and maintenance of tissue integrity), although their fate and function in these processes are unclear. In this study, we utilized lineage tracing, involving a novel MP-restricted knock-in line, to investigate liver MP biology. Single cell (sc) RNA-seq and ATAC-seq analyses show the existence of three distinct MP subpopulations. Using a liver fibrosis model in conjunction with single cell omics, we revealed that the three subpopulations undergo distinct activation profiles, leading to alterations in diverse, stage-specific transcriptional programs that modulate the liver stromal microenvironment. These findings provide vital insights into the contribution of MPs to liver homeostasis, regeneration and repair processes.