SOX2+ sustentacular cells are stem cells of the postnatal adrenal medulla

Alice Santambrogio, Yasmine Kemkem, Thea L. Willis, Ilona Berger, Maria Eleni Kastriti, Louis Faure, John P. Russell, Emily J. Lodge, Val Yianni, Bence Kövér, Rebecca J. Oakey, Barbara Altieri, Stefan R. Bornstein, Charlotte Steenblock, Igor Adameyko and Cynthia L. Andoniadou ()
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Alice Santambrogio: King’s College London
Yasmine Kemkem: King’s College London
Thea L. Willis: King’s College London
Ilona Berger: King’s College London
Maria Eleni Kastriti: Medical University Vienna
Louis Faure: Medical University Vienna
John P. Russell: King’s College London
Emily J. Lodge: King’s College London
Val Yianni: King’s College London
Bence Kövér: King’s College London
Rebecca J. Oakey: King’s College London
Barbara Altieri: University Hospital, University of Würzburg
Stefan R. Bornstein: Technische Universität Dresden
Charlotte Steenblock: Technische Universität Dresden
Igor Adameyko: Medical University Vienna
Cynthia L. Andoniadou: King’s College London

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Renewal of the catecholamine-secreting chromaffin cell population of the adrenal medulla is necessary for physiological homeostasis throughout life. Definitive evidence for the presence or absence of an adrenomedullary stem cell has been enigmatic. In this work, we demonstrate that a subset of sustentacular cells endowed with a support role, are in fact adrenomedullary stem cells. Through genetic tracing and comprehensive transcriptomic data of the mouse adrenal medulla, we show that cells expressing Sox2/SOX2 specialise as a unique postnatal population from embryonic Schwann Cell Precursors and are also present in the normal adult human adrenal medulla. Postnatal SOX2+ cells give rise to chromaffin cells of both the adrenaline and noradrenaline lineages in vivo and in vitro. We reveal that SOX2+ stem cells have a second, paracrine role in maintaining adrenal chromaffin cell homeostasis, where they promote proliferation through paracrine secretion of WNT6. This work identifies SOX2+ cells as a true stem cell for catecholamine-secreting chromaffin cells.

Date: 2025
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DOI: 10.1038/s41467-024-55289-5

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