Hematopoietic Cell Fate Reprogramming in the Context of Pathological Processes and Translational Opportunities

The hematopoietic system consists of well-characterized lineages that provide a diverse repertoire of cell subsets and highly specialized immune functions. This review summarizes the key characteristics and criteria that define hematopoietic cell fate conversion. Perturbation of lineage-specific transcription factors can enable cell fate reprogramming through transdifferentiation, dedifferentiation, or lineage diversion. Members of the CCAAT/enhancer binding protein family of transcription factors, which efficiently convert B cells into macrophages and neutrophils, serve here as a prime example for illustrating the underlying molecular processes. In addition, this review explores disease-associated phenomena, such as lineage infidelity in leukemia, and highlights novel therapeutic strategies that employ fate conversion. Controlled reprogramming systems can also serve as scalable and robust in vitro platforms for screening approaches and for dissecting functional mechanisms. Thus, hematopoietic cell fate reprogramming provides valuable insights into the specification of cellular identity and offers translational opportunities in immunity and cancer.