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bioRxiv · 10.1101/2021.12.22.473904

Single-cell RNA sequencing reveals a role for reactive oxygen species and peroxiredoxins in fatty-acid-induced rat β-cell proliferation

Vivoli, A.·Ghislain, J.·Filali-Mouhim, A.·Angeles, Z. E.·Castell, A.-L.·Sladek, R.·Poitout, V.
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Abstract

The functional mass of insulin-secreting pancreatic {beta} cells expands to maintain glucose homeostasis in the face of nutrient excess, in part via replication of existing {beta} cells. To decipher the underlying molecular mechanisms, we assessed {beta}-cell proliferation in isolated rat islets exposed to glucose and oleate or palmitate for 48 h and analyzed the transcriptional response by single-cell RNA sequencing. Unsupervised clustering of pooled {beta} cells identified subpopulations, including proliferating {beta} cells. {beta}-cell proliferation increased in response to oleate but not palmitate. Both fatty acids enhanced the expression of genes involved energy metabolism and mitochondrial activity. Comparison of proliferating vs. non-proliferating {beta} cells and pseudotime ordering suggested the involvement of reactive oxygen species (ROS) and peroxiredoxin signaling. Accordingly, the antioxidant N-acetyl cysteine and the peroxiredoxin inhibitor Conoidin A both blocked oleate-induced {beta}-cell proliferation. Our data reveal a key role for ROS signaling in {beta}-cell proliferation in response to nutrients.

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Vivoli, A., Ghislain, J., Filali-Mouhim, A., Angeles, Z. E., Castell, A.-L., Sladek, R., Poitout, V.. 2021-12-23. Single-cell RNA sequencing reveals a role for reactive oxygen species and peroxiredoxins in fatty-acid-induced rat β-cell proliferation. https://doi.org/10.1101/2021.12.22.473904

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