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Dev Cell. 2013 Sep 30;26(6):666-673. doi: 10.1016/j.devcel.2013.07.016. Epub 2013 Sep 12.

Adrenocortical zonation results from lineage conversion of differentiated zona glomerulosa cells.

Author information

1
Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115 USA.
2
Department of Pediatrics, Harvard Medical School, Boston, MA 02115 USA.
3
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908 USA.
4
Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216 USA.
5
Harvard Stem Cell Institute, Cambridge, MA 02138 USA.
#
Contributed equally

Abstract

Lineage conversion of differentiated cells in response to hormonal feedback has yet to be described. To investigate this, we studied the adrenal cortex, which is composed of functionally distinct concentric layers that develop postnatally, the outer zona glomerulosa (zG) and the inner zona fasciculata (zF). These layers have separate functions, are continuously renewed in response to physiological demands, and are regulated by discrete hormonal feedback loops. Their cellular origin, lineage relationship, and renewal mechanism, however, remain poorly understood. Cell-fate mapping and gene-deletion studies using zG-specific Cre expression demonstrate that differentiated zG cells undergo lineage conversion into zF cells. In addition, zG maintenance is dependent on the master transcriptional regulator Steroidogenic Factor 1 (SF-1), and zG-specific Sf-1 deletion prevents lineage conversion. These findings demonstrate that adrenocortical zonation and regeneration result from lineage conversion and may provide a paradigm for homeostatic cellular renewal in other tissues.

PMID:
24035414
PMCID:
PMC3791142
DOI:
10.1016/j.devcel.2013.07.016
[Indexed for MEDLINE]
Free PMC Article

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