Introduction to a review series on clonal tracking in hematopoiesis

Over the past decade, advances in single-cell genomics, lineage tracing, and computational phylogenetics have transformed our understanding of hematopoiesis by enabling detailed reconstruction of hematopoietic stem and progenitor cell clonal relationships across development and aging. Associate Editor Diane S. Krause introduces a comprehensive Review Series on the rapidly evolving field of clonal tracking in hematopoiesis. Rodriguez-Fraticelli outlines key experimental clonal analysis approaches and evaluates their strengths and limitations to guide appropriate method selection for specific biological questions. Tomei and colleagues synthesize clonal lineage–tracing studies to challenge the traditional hierarchical model of stem cell differentiation, proposing alternative frameworks in which lineage bias may arise early and multiple developmental pathways can produce the same mature cell types within phenotypically similar populations. Chen and coauthors explain how DNA methylation can serve as a heritable record of cell division to reconstruct clonal relationships in cancer and how integrating these signals with single-cell data enables reconstruction of tumor evolution while linking lineage history to cellular state and treatment response.