Adrenocortical Zonation Results from Lineage Conversion of Differentiated Zona Glomerulosa Cells

• Published in: Developmental cell Vol. 26; no. 6; pp. 666 - 673
• Main Authors: Freedman, Bethany D., Kempna, Petra Bukovac, Carlone, Diana L., Shah, Manasvi S., Guagliardo, Nick A., Barrett, Paula Q., Gomez-Sanchez, Celso E., Majzoub, Joseph A., Breault, David T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.09.2013
• Subjects: adrenal cortex; Animals; Cell Differentiation; Cell Lineage; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Feedback, Physiological; Gene Deletion; Gene Expression Regulation, Developmental; Homeostasis; Hormones - metabolism; Mice; physiological response; Steroidogenic Factor 1 - genetics; Steroidogenic Factor 1 - metabolism; tissues; transcription factors; Transcription, Genetic; Zona Fasciculata - cytology; Zona Fasciculata - growth & development; Zona Fasciculata - metabolism; Zona Glomerulosa - cytology; Zona Glomerulosa - growth & development; Zona Glomerulosa - metabolism
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2013.07.016

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. [Display omitted] •Homeostasis and regeneration involve lineage conversion of differentiated cells•Glomerulosa cell maintenance is dependent on the core transcriptional regulator SF1•An alternative pathway maintains zF cell production after loss of SF1 in zG cells Freedman et al. show that adrenocortical zonation during postnatal development, adult homeostasis, and tissue regeneration involves lineage conversion between differentiated cells in response to hormonal feedback. These findings underscore the plasticity of this vital organ and suggest that other adult tissues may also depend on lineage conversion for their maintenance.