ArticlebioRxiv : the preprint server for biology2025
Modular regulation of the stem cell transcriptome defines self-renewal, differentiation, and dedifferentiation.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Adult stem cells maintain tissue homeostasis by balancing self-renewal and differentiation. Stem cells themselves are frequently replenished by dedifferentiation of partially differentiated progeny. It is a paradox how stem cells and progeny retain the same potential to be or become stem cells, while undergoing different trajectories of self-renewal, differentiation, and dedifferentiation. Here, we show that Drosophila male germline stem cells (GSCs) solve this paradox via two parallel mechanisms. First, differentiating progeny (spermatogonia) may maintain dedifferentiation-competence by inheriting the transcriptome from GSCs in the form of perdurant mRNA, without actively transcribing these genes. Second, two niche signaling pathways (Bmp and Jak-Stat) activate overlapping but distinct subsets of transcriptional targets, and their combinatorial activity allows equally-potent cells to choose different trajectories. Together, this study reveals how a pool of dedifferentiation-competent progeny is maintained to regenerate stem cells as needed without resulting in tumorigenic stem cell overproduction.
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