title: Adrenocortical zonation results from lineage conversion of differentiated zona glomerulosa cells.
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.
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115 USA.|Department of Pediatrics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Bethany D
authors.initials: BD
authors.lastname: Freedman
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115 USA.|Department of Pediatrics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Petra Bukovac
authors.initials: PB
authors.lastname: Kempna
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115 USA.|Department of Pediatrics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Carlone
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115 USA.|Department of Pediatrics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Manasvi
authors.initials: M
authors.lastname: Shah
authors.affiliation: Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908 USA.
authors.forename: Nick A
authors.initials: NA
authors.lastname: Guagliardo
authors.affiliation: Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908 USA.
authors.forename: Paula Q
authors.initials: PQ
authors.lastname: Barrett
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216 USA.
authors.forename: Celso E
authors.initials: CE
authors.lastname: Gomez-Sanchez
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115 USA.|Department of Pediatrics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Majzoub
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115 USA.|Department of Pediatrics, Harvard Medical School, Boston, MA 02115 USA.|Harvard Stem Cell Institute, Cambridge, MA 02138 USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Breault
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D025461:Feedback, Physiological; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis; D006728:Hormones / Q000378:metabolism; D051379:Mice; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015383:Zona Fasciculata / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D015384:Zona Glomerulosa / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism
chemical_list: D006728:Hormones; D054339:Steroidogenic Factor 1
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