Multilineage-differentiating stress-enduring (Muse) cells, identified as cells positive for the pluripotent marker stage-specific embryonic antigen (SSEA-3+), were discovered as stress-tolerant pluripotent stem cells from among mesenchymal stem cells (MSCs) and fibroblasts, as well as from the adult human bone marrow mononucleated fraction. MSCs are a crude population of cells that differentiate into multiple cell types covering all three germ layers in low proportion and were thus deduced to contain a genuine pluripotent stem cell subpopulation. Muse cells constitute several percent of MSCs and 1 of ~3000 bone marrow mononucleated cells. They exhibit pluripotent gene expression as well as trilineage differentiation and self-renewal capabilities at the single-cell level, while, in contrast, MSC cells other than Muse cells do not exhibit these characteristics. These characteristics indicate that Muse cells correspond to the subpopulation of MSC cells responsible for the pluripotent aspect of MSCs. In addition to their pluripotency, Muse cells play an important role in vivo as endogenous stem cells that contribute to tissue homeostasis through daily reparative maintenance and to tissue reconstruction through their unique reparative functions following serious tissue damage. This chapter describes how my research team discovered Muse cells.