Single-cell ATAC-seq Reveals OVOL2 as a Downstream Negative Regulator of PRL-Mediated Proliferation in β-cells

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ID: 321038
2026
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Abstract
Maternal pancreatic β-cells undergo functional and structural changes to adapt to increased metabolic demands during pregnancy. Lactogen signaling via the prolactin receptor (PRLR) contributes to these adaptations by increasing β-cell mass, insulin transcription and glucose-stimulated insulin secretion. In other lactogen-responsive tissues such as the mammary glands and specific hypothalamic nuclei, gestation induces epigenetic changes, some of which persist long after birth. We have previously found that prolactin treatment in islets regulates the expression of epigenetic modifiers. However, whether lactogen signaling in β-cells mediates epigenetic changes to regulate chromatin accessibility has not been examined. Therefore, our objective was to determine whether PRLR signaling alters chromatin accessibility of β-cells to facilitate transcriptional regulation. Using single-cell ATAC-sequencing, we identified differentially accessible regions (DARs) in β-cells which had 718 overrepresented motifs following prolactin treatment of murine islets. Validating this approach, these included motifs bound by established PRLR signaling effectors such as the STAT family of transcription factors (TFs). Using RNA-sequencing we identified transcriptional changes in 41 TFs whose motifs were overrepresented in DARs, including several previously linked to PRLR signaling within β-cells, including Myc, Mafb and Esr1. Importantly, we also identified TFs not previously associated with PRLR signaling, including OVOL2 an established regulator of epigenetic landscape within cells. OVOL2 is a transcription factor involved in EMT inhibition and energy homeostasis with unknown roles in pancreatic β-cells. Here, we establish that OVOL2 acts as a negative regulator of lactogen-dependent effects on β-cell proliferation, establishing a novel regulator of PRLR signaling.
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openalex_W7168282436 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Nelmari Ruiz-Otero, Jin-Yong Chung, Ronadip R Banerjee
Journal american journal of physiology endocrinology and metabolism
Year 2026
DOI
10.1210/endocr/bqag080
URL
https://doi.org/10.1210/endocr/bqag080
Keywords Keywords not found

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