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bioRxiv · 10.1101/2025.01.16.633419

The epigenetic factor Zrf1 regulates intestinal stem cell proliferation during midgut regeneration

Li, J. S. S.·Liu, Y.·Kim, A.-R.·Qadiri, M.·Xu, J.·Xia, B.·Binari, R.·Asara, J. M.·Hu, Y.·Perrimon, N.
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Abstract

Stem cells are essential for tissue maintenance and regeneration, balancing self-renewal and differentiation to support homeostasis and repair. Through an RNAi screen in the Drosophila midgut, we identified the epigenetic factor Zrf1 as a critical regulator of intestinal stem cell (ISC) proliferation. Functional analyses reveal that Zrf1 integrates inputs from multiple signaling pathways and interacts with components of the RNA-induced silencing complex (RISC). Zrf1 mutants exhibit elevated expression of transposable elements (TEs) and chromatin disruption, highlighting a broader role in genome stability. Single-nuclei RNA sequencing (snRNA-seq) further demonstrated the influence of Zrf1 on chromatin organization and TE repression, particularly within stem cell progenitors. Our findings suggest that Zrf1 is potentially a key chromatin regulator necessary for maintaining stem cell proliferation and genome integrity, enhancing our understanding of the molecular controls underlying stem cell function and chromatin dynamics.

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Li, J. S. S., Liu, Y., Kim, A.-R., Qadiri, M., Xu, J., Xia, B., Binari, R., Asara, J. M., Hu, Y., Perrimon, N.. 2025-01-21. The epigenetic factor Zrf1 regulates intestinal stem cell proliferation during midgut regeneration. https://doi.org/10.1101/2025.01.16.633419

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