Exploiting somatic mutations to decipher human blood production: a natural lineage-tracing strategy

Lineage tracing using fluorescent proteins, genetic barcodes, and various other strategies has provided critical insights into the dynamics of both fetal and adult hematopoiesis in model organisms. However, these technologies cannot be readily used to study hematopoiesis in human beings. Therefore, there is a critical need to develop strategies to assess cellular dynamics within human hematopoietic tissues in vivo. Recently, researchers have used naturally acquired somatic mutations, coupled with other single-cell technologies, to retrospectively analyze clonal cellular dynamics. In summer 2022, the International Society for Experimental Hematology's New Investigator Committee hosted a webinar focused on novel approaches to dissect fetal and adult hematopoiesis, with presentations from Drs. Ana Cvejic and Vijay Sankaran. Here, we provide an overview of these exciting technological advances and some of the novel insights they have already provided in studying human hematopoiesis.