Cell Atlas at Single-Nuclei Resolution of the Adult Human Adrenal Gland and Adrenocortical Adenomas

Altieri, B.; Secener, K.; Sai, S.; Fischer, C.; Sbiera, S.; Arampatzi, P.; Herterich, S.; Landwehr, L.-S.; Vitcetz, S.; Braeuning, C.; Fassnacht, M.; Ronchi, C.; Sauer, S.

doi:10.1101/2022.08.27.505530

bioRxiv · 10.1101/2022.08.27.505530

Cell Atlas at Single-Nuclei Resolution of the Adult Human Adrenal Gland and Adrenocortical Adenomas

Altieri, B.·Secener, K.·Sai, S.·Fischer, C.·Sbiera, S.·Arampatzi, P.·Herterich, S.·Landwehr, L.-S.·Vitcetz, S.·Braeuning, C.·Fassnacht, M.·Ronchi, C.·Sauer, S.

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Abstract

The human adrenal gland is a complex endocrine tissue. Developmental studies on this tissue have been limited to animal models or human foetus. Here, we present a cell atlas analysis of the adult human normal adrenal gland, combining single-nuclei RNA sequencing and spatial transcriptome data to reconstruct adrenal gland development and tumourigenesis. We identified two populations of potential progenitor cells resident within the adrenal cortex: adrenocortical progenitors NR2F2+-ID1+ cells, located within and underneath the capsule, and medullary progenitors SYT1+-CHGA- cells, located in islets in the subcapsular region. Using pseudotime analyses, we provided evidence of the centripetal nature of adrenocortical cell development and of the essential role played by the Wnt/{beta}-catenin pathway in the adrenocortical self-renewal. By comparing transcriptional profiles of cells of normal adrenal glands and adrenocortical adenomas we revealed a high heterogeneity with six adenoma-specific clusters. Overall, our results give insights into adrenal plasticity and mechanisms underlying adrenocortical tumourigenesis.

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Altieri, B., Secener, K., Sai, S., Fischer, C., Sbiera, S., Arampatzi, P., Herterich, S., Landwehr, L.-S., Vitcetz, S., Braeuning, C., Fassnacht, M., Ronchi, C., Sauer, S.. 2022-08-28. Cell Atlas at Single-Nuclei Resolution of the Adult Human Adrenal Gland and Adrenocortical Adenomas. https://doi.org/10.1101/2022.08.27.505530

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