{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T01:50:14Z","timestamp":1783648214550,"version":"3.55.0"},"reference-count":54,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gatorade Trust Fund from the Department of Medicine, University of Florida Gatorade","award":["00122235"],"award-info":[{"award-number":["00122235"]}]},{"name":"Southeast Center for Integrated Metabolomics, University of Florida","award":["00122235"],"award-info":[{"award-number":["00122235"]}]},{"name":"Malcom Randall VA Pilot Award Program","award":["00122235"],"award-info":[{"award-number":["00122235"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The human adrenal cortex is composed of distinct zones that are the main source of steroid hormone production. The mechanism of adrenocortical cell differentiation into several functionally organized populations with distinctive identities remains poorly understood. Human adrenal disease has been difficult to study, in part due to the absence of cultured cell lines that faithfully represent adrenal cell precursors in the early stages of transformation. Here, Human Adrenocortical Adenoma (HAA1) cell line derived from a patient\u2019s macronodular adrenocortical hyperplasia and was treated with histone deacetylase inhibitors (HDACis) and gene expression was examined. We describe a patient-derived HAA1 cell line derived from the zona reticularis, the innermost zone of the adrenal cortex. The HAA1 cell line is unique in its ability to exit a latent state and respond with steroidogenic gene expression upon treatment with histone deacetylase inhibitors. The gene expression pattern of differentiated HAA1 cells partially recreates the roster of genes in the adrenal layer that they have been derived from. Gene ontology analysis of whole genome RNA-seq corroborated increased expression of steroidogenic genes upon HDAC inhibition. Surprisingly, HDACi treatment induced broad activation of the Tumor Necrosis Factor (TNF) alpha pathway. This novel cell line we developed will hopefully be instrumental in understanding the molecular and biochemical mechanisms controlling adrenocortical differentiation and steroidogenesis.<\/jats:p>","DOI":"10.3390\/ijms24010584","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T03:26:11Z","timestamp":1672370771000},"page":"584","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development of Human Adrenocortical Adenoma (HAA1) Cell Line from Zona Reticularis"],"prefix":"10.3390","volume":"24","author":[{"given":"Hans K.","family":"Ghayee","sequence":"first","affiliation":[{"name":"Division of Endocrinology & Metabolism, University of Florida, Gainesville, FL 32610, USA"},{"name":"Malcom Randall VAMC, Gainesville, FL 32608, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology & Metabolism, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3447-4688","authenticated-orcid":false,"given":"Heather","family":"Hatch","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, University of Florida, Gainesville, FL 32603, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Brockway","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, University of Florida, Gainesville, FL 32603, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asha S.","family":"Multani","sequence":"additional","affiliation":[{"name":"Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongjun","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3146-162X","authenticated-orcid":false,"given":"Wendy B.","family":"Bollag","sequence":"additional","affiliation":[{"name":"Charlie Norwood VA Medical Center, Augusta, GA 30904, USA"},{"name":"Department of Physiology, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adina","family":"Turcu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology & Metabolism, University of Michigan, Ann Arbor, MI 48109-5624, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Rainey","sequence":"additional","affiliation":[{"name":"Division of Endocrinology & Metabolism, University of Michigan, Ann Arbor, MI 48109-5624, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juilee","family":"Rege","sequence":"additional","affiliation":[{"name":"Division of Endocrinology & Metabolism, University of Michigan, Ann Arbor, MI 48109-5624, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutaka","family":"Nanba","sequence":"additional","affiliation":[{"name":"Division of Endocrinology & Metabolism, University of Michigan, Ann Arbor, MI 48109-5624, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikash J.","family":"Bhagwandin","sequence":"additional","affiliation":[{"name":"OncoStemyx, Inc., Palo Alto, CA 94401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiemu","family":"Nwariaku","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Stastny","sequence":"additional","affiliation":[{"name":"Hamon Center for Therapeutic Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8593, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi F.","family":"Gazdar","sequence":"additional","affiliation":[{"name":"Hamon Center for Therapeutic Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8593, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5052-0627","authenticated-orcid":false,"given":"Jerry W.","family":"Shay","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6815-6181","authenticated-orcid":false,"given":"Richard J.","family":"Auchus","sequence":"additional","affiliation":[{"name":"Division of Endocrinology & Metabolism, University of Michigan, Ann Arbor, MI 48109-5624, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei G.","family":"Tevosian","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, University of Florida, Gainesville, FL 32603, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1538\/expanim.44.285","article-title":"Comparison of adrenocortical zonation in C57BL\/6J and DDD mice","volume":"44","author":"Tanaka","year":"1995","journal-title":"Exp. 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