Hematopoietic Stem Cell States, Function, and Molecular Identity: From Quantitative Assays to Modern Multiomics.

Hematopoietic stem and progenitor cells (HSPCs) are characterized by the ability to proliferate, differentiate into multiple lineages, self-renew, and repopulate the hematopoietic system. Development of functional assays enabling qualitative and quantitative measurements of these different features are cornerstones of the field. In this review, we summarize key approaches from early transplantation and spleen colony-forming unit assays to in vitro clonogenic systems, long-term culture assays, xenotransplantation models, and single-cell platforms with historical perspectives and evaluation of their utilities as well as limitations. We emphasize the principles of functional definition of stem and progenitor cells and the discoveries of clonal origin and functional heterogeneity within phenotypically defined HSPC populations.