Hematopoietic cell reprogramming, defined as the conversion from one hematopoietic or immune cell type into another, has been shown to hold transformative potential for advancing our understanding of hematopoiesis, disease mechanisms, and therapeutic innovation. This process occurs via transdifferentiation, dedifferentiation, or transitional plasticity, driven by transcriptional, epigenetic, and microenvironmental cues, which may be achieved by physiological or pathological stressors in vivo, or genetic or chemical strategies in vitro. Nevertheless, challenges persist, including low reprogramming efficiency, unstable phenotype, and safety concerns. Advancements in multi-omics, gene editing, and chemical biology are enhancing the efficacy of reprogramming protocols and facilitating clinical translatability. The integration of these strategies, in conjunction with artificial intelligence-driven screening and single-cell analytics, has the potential to facilitate the development of personalized cell therapies for cancers, immune disorders, and regenerative medicine. Additionally, the realization of this potential is contingent upon the resolution of challenges related to delivery, specificity, and long-term efficacy.
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