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Post-larval hematopoiesis in Drosophila largely depends upon the stockpile of progenitors present in the blood-forming organ/lymph gland of the larvae. During larval stages, the lymph gland progenitors gradually accumulate reactive oxygen species (ROS), which is essential to prime them for differentiation. Studies have shown that ROS triggers the activation of JNK (c-Jun Kinase), which upregulates fatty acid oxidation (FAO) to facilitate progenitor differentiation. Intriguingly, despite having ROS, the entire progenitor pool does not differentiate simultaneously in the late larval stages. Using expression analyses, genetic manipulation and pharmacological approaches, we found that the Drosophila NF-κB transcription factor Relish (Rel) shields the progenitor pool from the metabolic pathway that inducts them into the differentiation program by curtailing the activation of JNK. Although ROS serves as the metabolic signal for progenitor differentiation, the input from ROS is monitored by the developmental signal TAK1, which is regulated by Relish. This developmental circuit ensures that the stockpile of ROS-primed progenitors is not exhausted entirely. Our study sheds light on how, during development, integrating NF-κB-like factors with metabolic pathways seem crucial to regulating cell fate transition during development. Author summary: The determination of cell fate in stem/progenitor cells is crucial for normal development and various pathophysiological conditions. Our research focuses on the Drosophila larval blood-forming organ, the lymph gland, as a model to gain further insights into this intricate process. Interestingly, while the entire progenitor pool within this organ is enriched in Reactive Oxygen Species (ROS), which is a known trigger for differentiation, they do not differentiate entirely. We show that Relish, a component of the Immune Deficiency Pathway (IMD), plays a role in preventing premature differentiation of the progenitors. Relish hinders TAK1 (transforming growth factor-β-activated kinase 1), thereby reducing JNK activation downstream of ROS. This inhibition on JNK delays progenitor differentiation. Our study reveals an interplay between developmental signaling and metabolic factors that govern the fate specification and maintenance of blood progenitors. Given that the process of blood development in flies shares several similarities with mammalian hematopoiesis, including the presence of high ROS in the myeloid progenitors, it would be worth exploring whether similar interactions are at play in vertebrate hematopoiesis. In addition, it would be fascinating to investigate whether similar coordination between metabolic and developmental signals regulates the differentiation of stem/progenitor cells in other biological systems. [ABSTRACT FROM AUTHOR]