1. SOX2 + sustentacular cells are stem cells of the postnatal adrenal medulla.
- Author
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Santambrogio A, Kemkem Y, Willis TL, Berger I, Kastriti ME, Faure L, Russell JP, Lodge EJ, Yianni V, Kövér B, Oakey RJ, Altieri B, Bornstein SR, Steenblock C, Adameyko I, and Andoniadou CL
- Subjects
- Animals, Humans, Mice, Cell Proliferation, Cell Differentiation, Catecholamines metabolism, Schwann Cells metabolism, Schwann Cells cytology, Female, Male, Paracrine Communication, Adrenal Medulla cytology, Adrenal Medulla metabolism, Chromaffin Cells metabolism, Chromaffin Cells cytology, SOXB1 Transcription Factors metabolism, SOXB1 Transcription Factors genetics, Stem Cells metabolism, Stem Cells cytology
- 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., Competing Interests: Competing interests: A.S. and T.L.W. are currently employees of Altos Labs. V.Y. is currently an employee of Bit.bio. I.B. is currently an employee of Novartis. The remaining authors declare no competing interests., (© 2024. The Author(s).)- Published
- 2025
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