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  • Review Article
  • Published:

Regulation of the adrenocortical stem cell niche: implications for disease

Nature Reviews Endocrinology volume 11, pages 14–28 (2015)Cite this article

Subjects

Key Points

  • Fetal adrenal cells are critical for the establishment of the capsular–cortical unit of the adrenal gland; these cells populate the mesenchymal capsule to become stem cells for the underlying adult (definitive) cortex

  • The adrenal capsular and subcapsular cell populations have a crucial role in gland maintenance; paracrine signals between the capsule and the cortex coordinate normal homeostasis by regulating capsular and subcapsular cellular lineages

  • Genetic defects in signalling pathways that regulate adrenocortical stem and progenitor cells contribute to diseases across the spectrum of adrenal failure and neoplasia

Abstract

Stem cells are endowed with the potential for self-renewal and multipotency. Pluripotent embryonic stem cells have an early role in the formation of the three germ layers (ectoderm, mesoderm and endoderm), whereas adult tissue stem cells and progenitor cells are critical mediators of organ homeostasis. The adrenal cortex is an exceptionally dynamic endocrine organ that is homeostatically maintained by paracrine and endocrine signals throughout postnatal life. In the past decade, much has been learned about the stem and progenitor cells of the adrenal cortex and the multiple roles that these cell populations have in normal development and homeostasis of the adrenal gland and in adrenal diseases. In this Review, we discuss the evidence for the presence of adrenocortical stem cells, as well as the various signalling molecules and transcriptional networks that are critical for the embryological establishment and postnatal maintenance of this vital population of cells. The implications of these pathways and cells in the pathophysiology of disease are also addressed.

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Figure 1: Cell lineages in adrenal gland development and homeostasis.
Figure 2: Simplified view of the adrenocortical homeostatic unit.
Figure 3: Paracrine and endocrine signals that act on adrenocortical cells.

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Acknowledgements

We thank J. Heaton (University of Michigan, Ann Arbor, MI, USA) for helpful discussions and critical reading of the manuscript.

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Authors and Affiliations

  1. Division of Nephrology, School of Medicine, Stanford University, Stanford, 94305, CA, USA

    Elisabeth M. Walczak

  2. Center for Organogenesis, Alfred Taubman Biomedical Sciences Research Building, Room 1528, 109 Zina Pitcher Place, Ann Arbor, 48109-2200, MI, USA

    Gary D. Hammer

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E.M.W. researched the data for the article and wrote the article. E.M.W. and G.D.H. contributed equally to discussion of the content of the article and to review and/or editing of the manuscript before submission.

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Correspondence to Gary D. Hammer.

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Walczak, E., Hammer, G. Regulation of the adrenocortical stem cell niche: implications for disease. Nat Rev Endocrinol 11, 14–28 (2015). https://doi.org/10.1038/nrendo.2014.166

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