Notch Signaling Drives Pro-Regenerative and Migratory Traits in Glandular Stem/Progenitor Cells

Cinat, D.; Maturi, R.; Gunawan, J. P.; Jellema-de Bruin, A. L.; Kracht, L.; Martinez, P. S.; Wu, Y.; Soto-Gamez, A.; van Goethem, M.-J.; Holtman, I. R.; Pringle, S.; Barazzuol, L.; Coppes, R. P.

doi:10.1101/2024.11.27.625738

bioRxiv · 10.1101/2024.11.27.625738

Notch Signaling Drives Pro-Regenerative and Migratory Traits in Glandular Stem/Progenitor Cells

Cinat, D.·Maturi, R.·Gunawan, J. P.·Jellema-de Bruin, A. L.·Kracht, L.·Martinez, P. S.·Wu, Y.·Soto-Gamez, A.·van Goethem, M.-J.·Holtman, I. R.·Pringle, S.·Barazzuol, L.·Coppes, R. P.

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Abstract

Organoid models have advanced our understanding of adult stem/progenitor cell dynamics and function. However, uncovering the regulatory mechanisms of scarce and often quiescent stem cells in organs like the salivary glands remains challenging. Using single-cell RNA sequencing and bulk ATAC and RNA-sequencing analysis, we conducted in-depth profiling of the cellular populations and key signaling pathways characterizing a mouse submandibular salivary gland organoid (mSGO) model at different temporal stages and in response to radiation damage. We identified Sox9- and Itgb1-expressing cells as the most primitive adult stem/progenitor populations and uncover novel stemness and migratory roles for Cd44-expressing cells. Moreover, we revealed that Notch signaling is essential for maintaining self-renewal and migration potential of these stem/progenitor cells post-irradiation. Extending these findings to patient-derived mSGOs, as well as murine and patient-derived mammary and thyroid gland organoids, we confirmed Notch signaling as a conserved regulator of stem/progenitor cell function under migrative and regenerative conditions.

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Cinat, D., Maturi, R., Gunawan, J. P., Jellema-de Bruin, A. L., Kracht, L., Martinez, P. S., Wu, Y., Soto-Gamez, A., van Goethem, M.-J., Holtman, I. R., Pringle, S., Barazzuol, L., Coppes, R. P.. 2024-11-28. Notch Signaling Drives Pro-Regenerative and Migratory Traits in Glandular Stem/Progenitor Cells. https://doi.org/10.1101/2024.11.27.625738

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