Heterogeneity in cell-cycle dynamics of synthetic mRNA-induced β-cell proliferation

Authors

Bittenglova, K., Zacharovova, K., Tichanek, F., Leontovyc, I., Girman, P., Kriz, J., Saudek, F., Koblas, T.

Abstract

Adult pancreatic {beta}-cells are mostly locked in quiescence, limiting large-scale analysis of their cell cycle. To overcome this limitation, we used synthetic in vitro transcribed mRNAs encoding Cyclin D1 and CDK4 to induce proliferation in up to 70% of primary rat {beta}-cells. Flow cytometry-based analysis of cell-cycle markers revealed substantial heterogeneity in {beta}-cell cell-cycle progression, identifying five distinct groups of proliferating {beta}-cells based on G1 entry timing. Total cell-cycle length ranged from approximately 26 to 34 hours and was primarily determined by variability in G1 duration (13-19 hours). In the fastest-dividing {beta}-cells, G1, S, and G2M lasted approximately 13, 6, and 7 hours, respectively, whereas later-entering {beta}-cells exhibited progressively longer G1 phase. Additionally, we identified a small {beta}-cell subpopulation that failed to complete division and may have exited the cell cycle. These findings reveal cell-cycle entry and G1 progression as a major source of heterogeneity in {beta}-cell proliferation and provide quantitative benchmark for developing strategies to enhance controlled {beta}-cell regeneration in diabetes.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 15 Sep 2026.

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