Abstract
Hematopoietic stem and progenitor cells (HSPCs) form the foundation of lifelong blood cell production and immune function. Understanding their fate, including how they differentiate, self-renew, and respond to environmental cues has long been a cornerstone of stem cell biology and regenerative medicine. This knowledge is especially vital in the context of therapeutic hematopoietic stem and progenitor cell transplantation, where the diverse behavior of transplanted HSPCs directly impacts patient outcomes. Advances in single-cell omics, lineage barcoding, and in situ tracking now allow us to directly trace the developmental trajectories and clonal contributions of individual HSPCs. These tools are reshaping our understanding of hematopoiesis not as a rigid hierarchy but as a dynamic and adaptive system. This review highlights key technologies that enable fate mapping of HSPCs, integrates insights into clonal behavior during both transplantation and native hematopoiesis, and discusses how these findings are likely to inform future diagnostic and therapeutic strategies. CLINICAL TRIAL NUMBER: Not applicable.