Adrenocortical stem cells in health and disease

Yates, R. et al. Adrenocortical development, maintenance, and disease. Curr. Top. Dev. Biol. 106, 239–312 (2013).
Google Scholar
Tsilosani, A., Gao, C. & Zhang, W. Aldosterone-regulated sodium transport and blood pressure. Front. Physiol. 13, 770375 (2022).
Google Scholar
Douglass, A. M. et al. Neural basis for fasting activation of the hypothalamic–pituitary–adrenal axis. Nature 620, 154–162 (2023).
Google Scholar
Matzke, C. C., Kusch, J. M., Janz, D. M. & Lane, J. E. Perceived predation risk predicts glucocorticoid hormones, but not reproductive success in a colonial rodent. Horm. Behav. 143, 105200 (2022).
Google Scholar
Wirth, M. M. Hormones, stress, and cognition: the effects of glucocorticoids and oxytocin on memory. Adapt. Hum. Behav. Physiol. 1, 177–201 (2015).
Google Scholar
Li, J. X. & Cummins, C. L. Fresh insights into glucocorticoid-induced diabetes mellitus and new therapeutic directions. Nat. Rev. Endocrinol. 18, 540–557 (2022).
Google Scholar
Nguyen, T. V. et al. Interactive effects of dehydroepiandrosterone and testosterone on cortical thickness during early brain development. J. Neurosci. 33, 10840–10848 (2013).
Google Scholar
Dumontet, T. & Martinez, A. Adrenal androgens, adrenarche, and zona reticularis: a human affair? Mol. Cell Endocrinol. 528, 111239 (2021).
Google Scholar
Hammer, G. D. & Basham, K. J. Stem cell function and plasticity in the normal physiology of the adrenal cortex. Mol. Cell Endocrinol. 519, 111043 (2021).
Google Scholar
Lerario, A. M., Moraitis, A. & Hammer, G. D. Genetics and epigenetics of adrenocortical tumors. Mol. Cell Endocrinol. 386, 67–84 (2014).
Google Scholar
Scheys, J. O., Heaton, J. H. & Hammer, G. D. Evidence of adrenal failure in aging Dax1-deficient mice. Endocrinology 152, 3430–3439 (2011).
Google Scholar
Cheng, K. et al. The developmental origin and the specification of the adrenal cortex in humans and cynomolgus monkeys. Sci. Adv. 8, eabn8485 (2022).
Google Scholar
Ross, I. L. & Louw, G. J. Embryological and molecular development of the adrenal glands. Clin. Anat. 28, 235–242 (2015).
Google Scholar
Bandiera, R. et al. WT1 maintains adrenal-gonadal primordium identity and marks a population of AGP-like progenitors within the adrenal gland. Dev. Cell 27, 5–18 (2013).
Google Scholar
Neirijnck, Y. et al. Single-cell transcriptomic profiling redefines the origin and specification of early adrenogonadal progenitors. Cell Rep. 42, 112191 (2023).
Google Scholar
Kim, J. H. & Choi, M. H. Embryonic development and adult regeneration of the adrenal gland. Endocrinol. Metab. 35, 765–773 (2020).
Google Scholar
Val, P., Martinez-Barbera, J. P. & Swain, A. Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage. Development 134, 2349–2358 (2007).
Google Scholar
Moore, A. W., McInnes, L., Kreidberg, J., Hastie, N. D. & Schedl, A. YAC complementation shows a requirement for Wt1 in the development of epicardium, adrenal gland and throughout nephrogenesis. Development 126, 1845–1857 (1999).
Google Scholar
Bamforth, S. D. et al. Cardiac malformations, adrenal agenesis, neural crest defects and exencephaly in mice lacking Cited2, a new Tfap2 co-activator. Nat. Genet. 29, 469–474 (2001).
Google Scholar
Parker, K. L. & Schimmer, B. P. Steroidogenic factor 1: a key determinant of endocrine development and function. Endocr. Rev. 18, 361–377 (1997).
Google Scholar
Abou Nader, N. & Boyer, A. Adrenal cortex development and maintenance: knowledge acquired from mouse models. Endocrinology 162, bqab187 (2021).
Google Scholar
Akkuratova, N., Faure, L., Kameneva, P., Kastriti, M. E. & Adameyko, I. Developmental heterogeneity of embryonic neuroendocrine chromaffin cells and their maturation dynamics. Front. Endocrinol. 13, 1020000 (2022).
Google Scholar
Ishimoto, H. & Jaffe, R. B. Development and function of the human fetal adrenal cortex: a key component in the feto-placental unit. Endocr. Rev. 32, 317–355 (2011).
Google Scholar
King, P., Paul, A. & Laufer, E. Shh signaling regulates adrenocortical development and identifies progenitors of steroidogenic lineages. Proc. Natl Acad. Sci. USA 106, 21185–21190 (2009).
Google Scholar
Wood, M. A. et al. Fetal adrenal capsular cells serve as progenitor cells for steroidogenic and stromal adrenocortical cell lineages in M. musculus. Development 140, 4522–4532 (2013).
Google Scholar
Finco, I., Lerario, A. M. & Hammer, G. D. Sonic Hedgehog and WNT signaling promote adrenal gland regeneration in male mice. Endocrinology 159, 579–596 (2018).
Google Scholar
Huang, C. C., Miyagawa, S., Matsumaru, D., Parker, K. L. & Yao, H. H. Progenitor cell expansion and organ size of mouse adrenal is regulated by sonic hedgehog. Endocrinology 151, 1119–1128 (2010).
Google Scholar
Zubair, M., Parker, K. L. & Morohashi, K. Developmental links between the fetal and adult zones of the adrenal cortex revealed by lineage tracing. Mol. Cell Biol. 28, 7030–7040 (2008).
Google Scholar
Ingham, P. W. Hedgehog signaling. Curr. Top. Dev. Biol. 149, 1–58 (2022).
Google Scholar
Grainger, S. & Willert, K. Mechanisms of Wnt signaling and control. Wiley Interdiscip. Rev. Syst. Biol. Med. 10, e1422 (2018).
Google Scholar
Vidal, V. et al. The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3. Genes. Dev. 30, 1389–1394 (2016).
Google Scholar
Kim, J. E. et al. Single cell and genetic analyses reveal conserved populations and signaling mechanisms of gastrointestinal stromal niches. Nat. Commun. 11, 334 (2020).
Google Scholar
Drelon, C., Berthon, A., Mathieu, M., Martinez, A. & Val, P. Adrenal cortex tissue homeostasis and zonation: a WNT perspective. Mol. Cell Endocrinol. 408, 156–164 (2015).
Google Scholar
Lucas, C. et al. Loss of LGR4/GPR48 causes severe neonatal salt wasting due to disrupted WNT signaling altering adrenal zonation. J. Clin. Invest. 133, e164915 (2023).
Google Scholar
Hasenmajer, V. et al. Rare forms of genetic paediatric adrenal insufficiency: excluding congenital adrenal hyperplasia. Rev. Endocr. Metab. Disord. 24, 345–363 (2023).
Google Scholar
Basham, K. J. et al. A ZNRF3-dependent Wnt/beta-catenin signaling gradient is required for adrenal homeostasis. Genes Dev. 33, 209–220 (2019).
Google Scholar
Drelon, C. et al. PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development. Nat. Commun. 7, 12751 (2016).
Google Scholar
Schulte, D. M., Shapiro, I., Reincke, M. & Beuschlein, F. Expression and spatio-temporal distribution of differentiation and proliferation markers during mouse adrenal development. Gene Expr. Patterns 7, 72–81 (2007).
Google Scholar
Zubair, M., Ishihara, S., Oka, S., Okumura, K. & Morohashi, K. Two-step regulation of Ad4BP/SF-1 gene transcription during fetal adrenal development: initiation by a Hox–Pbx1–Prep1 complex and maintenance via autoregulation by Ad4BP/SF-1. Mol. Cell Biol. 26, 4111–4121 (2006).
Google Scholar
Pihlajoki, M., Dorner, J., Cochran, R. S., Heikinheimo, M. & Wilson, D. B. Adrenocortical zonation, renewal, and remodeling. Front. Endocrinol. 6, 27 (2015).
Google Scholar
Havelock, J. C., Auchus, R. J. & Rainey, W. E. The rise in adrenal androgen biosynthesis: adrenarche. Semin. Reprod. Med. 22, 337–347 (2004).
Google Scholar
Freedman, B. D. et al. Adrenocortical zonation results from lineage conversion of differentiated zona glomerulosa cells. Dev. Cell 26, 666–673 (2013).
Google Scholar
Zajicek, G., Ariel, I. & Arber, N. The streaming adrenal cortex: direct evidence of centripetal migration of adrenocytes by estimation of cell turnover rate. J. Endocrinol. 111, 477–482 (1986).
Google Scholar
Dumontet, T. et al. PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal. JCI Insight 3, e98394 (2018).
Google Scholar
Grabek, A. et al. The adult adrenal cortex undergoes rapid tissue renewal in a sex-specific manner. Cell Stem Cell 25, 290–296 e292 (2019).
Google Scholar
Kim, A. C. et al. Targeted disruption of beta-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex. Development 135, 2593–2602 (2008).
Google Scholar
Borges, K. S. et al. Non-canonical Wnt signaling triggered by WNT2B drives adrenal aldosterone production. Preprint at bioRxiv (2024).
Nishimoto, K., Harris, R. B., Rainey, W. E. & Seki, T. Sodium deficiency regulates rat adrenal zona glomerulosa gene expression. Endocrinology 155, 1363–1372 (2014).
Google Scholar
Bielohuby, M. et al. Growth analysis of the mouse adrenal gland from weaning to adulthood: time- and gender-dependent alterations of cell size and number in the cortical compartment. Am. J. Physiol. Endocrinol. Metab. 293, E139–E146 (2007).
Google Scholar
Holland, J. H. Signals and Boundaries: Building Blocks for Complex Adaptive Systems (MIT Press, 2014).
Chu, Y., Xing, Y. & Hammer, G. Unravelling the role of CDK7-mediated SF1 serine 203 phosphorylation in adrenal homeostasis. J. Endocr. Soc. 6, A135–A136 (2022).
Google Scholar
Sandhoff, T. W. & McLean, M. P. Repression of the rat steroidogenic acute regulatory (StAR) protein gene by PGF2α is modulated by the negative transcription factor DAX-1. Endocrine 10, 83–91 (1999).
Google Scholar
Khalfallah, O., Rouleau, M., Barbry, P., Bardoni, B. & Lalli, E. Dax-1 knockdown in mouse embryonic stem cells induces loss of pluripotency and multilineage differentiation. Stem Cell 27, 1529–1537 (2009).
Google Scholar
Zhang, J. et al. Dax1 and Nanog act in parallel to stabilize mouse embryonic stem cells and induced pluripotency. Nat. Commun. 5, 5042 (2014).
Google Scholar
Zhang, W. et al. nr0b1 (DAX1) loss of function in zebrafish causes hypothalamic defects via abnormal progenitor proliferation and differentiation. J. Genet. Genomics 49, 217–229 (2022).
Google Scholar
Achermann, J. C., Silverman, B. L., Habiby, R. L. & Jameson, J. L. Presymptomatic diagnosis of X-linked adrenal hypoplasia congenita by analysis of DAX1. J. Pediatr. 137, 878–881 (2000).
Google Scholar
Gummow, B. M., Scheys, J. O., Cancelli, V. R. & Hammer, G. D. Reciprocal regulation of a glucocorticoid receptor-steroidogenic factor-1 transcription complex on the Dax-1 promoter by glucocorticoids and adrenocorticotropic hormone in the adrenal cortex. Mol. Endocrinol. 20, 2711–2723 (2006).
Google Scholar
Ganuza, M. et al. Genetic inactivation of Cdk7 leads to cell cycle arrest and induces premature aging due to adult stem cell exhaustion. EMBO J. 31, 2498–2510 (2012).
Google Scholar
Leal, L. F. et al. Inhibition of the Tcf/β-catenin complex increases apoptosis and impairs adrenocortical tumor cell proliferation and adrenal steroidogenesis. Oncotarget 6, 43016–43032 (2015).
Google Scholar
Chu, Y., Ho, W. J. & Dunn, J. C. Basic fibroblast growth factor delivery enhances adrenal cortical cellular regeneration. Tissue Eng. A 15, 2093–2101 (2009).
Google Scholar
Looyenga, B. D. & Hammer, G. D. Origin and identity of adrenocortical tumors in inhibin knockout mice: implications for cellular plasticity in the adrenal cortex. Mol. Endocrinol. 20, 2848–2863 (2006).
Google Scholar
Ornitz, D. M. & Itoh, N. The fibroblast growth factor signaling pathway. Wiley Interdiscip. Rev. Dev. Biol. 4, 215–266 (2015).
Google Scholar
Forbes, B. E., Blyth, A. J. & Wit, J. M. Disorders of IGFs and IGF-1R signaling pathways. Mol. Cell Endocrinol. 518, 111035 (2020).
Google Scholar
Mesiano, S., Mellon, S. H. & Jaffe, R. B. Mitogenic action, regulation, and localization of insulin-like growth factors in the human fetal adrenal gland. J. Clin. Endocrinol. Metab. 76, 968–976 (1993).
Google Scholar
Basile, D. P. & Holzwarth, M. A. Basic fibroblast growth factor may mediate proliferation in the compensatory adrenal growth response. Am. J. Physiol. 265, R1253–R1261 (1993).
Google Scholar
Lepique, A. P. et al. c-Myc protein is stabilized by fibroblast growth factor 2 and destabilized by ACTH to control cell cycle in mouse Y1 adrenocortical cells. J. Mol. Endocrinol. 33, 623–638 (2004).
Google Scholar
Gospodarowicz, D., Ill, C. R., Hornsby, P. J. & Gill, G. N. Control of bovine adrenal cortical cell proliferation by fibroblast growth factor. Lack of effect of epidermal growth factor. Endocrinology 100, 1080–1089 (1977).
Google Scholar
Crickard, K., Ill, C. R. & Jaffe, R. B. Control of proliferation of human fetal adrenal cells in vitro. J. Clin. Endocrinol. Metab. 53, 790–796 (1981).
Google Scholar
Gospodarowicz, D. & Handley, H. H. Stimulation of division of Y1 adrenal cells by a growth factor isolated from bovine pituitary glands. Endocrinology 97, 102–107 (1975).
Google Scholar
Guasti, L., Candy Sze, W. C., McKay, T., Grose, R. & King, P. J. FGF signalling through Fgfr2 isoform IIIb regulates adrenal cortex development. Mol. Cell Endocrinol. 371, 182–188 (2013).
Google Scholar
Kim, Y. et al. Fibroblast growth factor receptor 2 regulates proliferation and Sertoli differentiation during male sex determination. Proc. Natl Acad. Sci. USA 104, 16558–16563 (2007).
Google Scholar
Hafner, R., Bohnenpoll, T., Rudat, C., Schultheiss, T. M. & Kispert, A. Fgfr2 is required for the expansion of the early adrenocortical primordium. Mol. Cell Endocrinol. 413, 168–177 (2015).
Google Scholar
Laufer, E., Kesper, D., Vortkamp, A. & King, P. Sonic hedgehog signaling during adrenal development. Mol. Cell Endocrinol. 351, 19–27 (2012).
Google Scholar
Else, T. et al. Adrenocortical carcinoma. Endocr. Rev. 35, 282–326 (2014).
Google Scholar
Nanba, K. et al. Molecular heterogeneity in aldosterone-producing adenomas. J. Clin. Endocrinol. Metab. 101, 999–1007 (2016).
Google Scholar
Fassnacht, M. et al. European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur. J. Endocrinol. 179, G1–G46 (2018).
Google Scholar
Scadden, D. T. Nice neighborhood: emerging concepts of the stem cell niche. Cell 157, 41–50 (2014).
Google Scholar
Hoggatt, J., Kfoury, Y. & Scadden, D. T. Hematopoietic stem cell niche in health and disease. Annu. Rev. Pathol. 11, 555–581 (2016).
Google Scholar
Zheng, S. et al. Comprehensive pan-genomic characterization of adrenocortical carcinoma. Cancer Cell 29, 723–736 (2016).
Google Scholar
Gomes, D. C. et al. Sonic hedgehog signaling is active in human adrenal cortex development and deregulated in adrenocortical tumors. J. Clin. Endocrinol. Metab. 99, E1209–E1216 (2014).
Google Scholar
Boulkroun, S. et al. Aldosterone-producing adenoma formation in the adrenal cortex involves expression of stem/progenitor cell markers. Endocrinology 152, 4753–4763 (2011).
Google Scholar
Goh, G. et al. Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors. Nat. Genet. 46, 613–617 (2014).
Google Scholar
Marquardt, A. et al. Identifying new potential biomarkers in adrenocortical tumors based on mRNA expression data using machine learning. Cancers 13, 4671 (2021).
Google Scholar
Mohan, D. R. et al. β-catenin-driven differentiation is a tissue-specific epigenetic vulnerability in adrenal cancer. Cancer Res. 83, 2123–2141 (2023).
Google Scholar
Heaton, J. H. et al. Progression to adrenocortical tumorigenesis in mice and humans through insulin-like growth factor 2 and β-catenin. Am. J. Pathol. 181, 1017–1033 (2012).
Google Scholar
Pinto, E. M. et al. Genomic landscape of paediatric adrenocortical tumours. Nat. Commun. 6, 6302 (2015).
Google Scholar
Werminghaus, P. et al. Hedgehog-signaling is upregulated in non-producing human adrenal adenomas and antagonism of hedgehog-signaling inhibits proliferation of NCI-H295R cells and an immortalized primary human adrenal cell line. J. Steroid Biochem. Mol. Biol. 139, 7–15 (2014).
Google Scholar
Mateska, I., Nanda, K., Dye, N. A., Alexaki, V. I. & Eaton, S. Range of SHH signaling in adrenal gland is limited by membrane contact to cells with primary cilia. J. Cell Biol. 219, e201910087 (2020).
Google Scholar
Borges, K. S. et al. Wnt/β-catenin activation cooperates with loss of p53 to cause adrenocortical carcinoma in mice. Oncogene 39, 5282–5291 (2020).
Google Scholar
Berthon, A. et al. Constitutive β-catenin activation induces adrenal hyperplasia and promotes adrenal cancer development. Hum. Mol. Genet. 19, 1561–1576 (2010).
Google Scholar
Wilmouth, J. J. Jr. et al. Sexually dimorphic activation of innate antitumor immunity prevents adrenocortical carcinoma development. Sci. Adv. 8, eadd0422 (2022).
Google Scholar
Reutens, A. T. et al. Clinical and functional effects of mutations in the DAX-1 gene in patients with adrenal hypoplasia congenita. J. Clin. Endocrinol. Metab. 84, 504–511 (1999).
Google Scholar
Lyraki, R. et al. Crosstalk between androgen receptor and WNT/β-catenin signaling causes sex-specific adrenocortical hyperplasia in mice. Dis. Model. Mech. 16, dmm050053 (2023).
Google Scholar
Kamilaris, C. D. C., Hannah-Shmouni, F. & Stratakis, C. A. Adrenocortical tumorigenesis: lessons from genetics. Best Pract. Res. Clin. Endocrinol. Metab. 34, 101428 (2020).
Google Scholar
Lapunzina, P. Risk of tumorigenesis in overgrowth syndromes: a comprehensive review. Am. J. Med. Genet. C 137C, 53–71 (2005).
Google Scholar
Husebye, E. S., Pearce, S. H., Krone, N. P. & Kampe, O. Adrenal insufficiency. Lancet 397, 613–629 (2021).
Google Scholar
Holmes, L. A survey of bar coding in Canadian teaching hospitals. Dimens. Health Serv. 64, 23–25 (1987).
Google Scholar
Ferraz-de-Souza, B., Lin, L. & Achermann, J. C. Steroidogenic factor-1 (SF-1, NR5A1) and human disease. Mol. Cell Endocrinol. 336, 198–205 (2011).
Google Scholar
Bland, M. L. et al. Haploinsufficiency of steroidogenic factor-1 in mice disrupts adrenal development leading to an impaired stress response. Proc. Natl Acad. Sci. USA 97, 14488–14493 (2000).
Google Scholar
Arboleda, V. A. et al. Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome. Nat. Genet. 44, 788–792 (2012).
Google Scholar
Ma, Y. et al. CDKN1C negatively regulates RNA polymerase II C-terminal domain phosphorylation in an E2F1-dependent manner. J. Biol. Chem. 285, 9813–9822 (2010).
Google Scholar
Lewis, A. E. et al. Phosphorylation of steroidogenic factor 1 is mediated by cyclin-dependent kinase 7. Mol. Endocrinol. 22, 91–104 (2008).
Google Scholar
Alheim, K. et al. Identification of a functional glucocorticoid response element in the promoter of the cyclin-dependent kinase inhibitor p57Kip2. J. Mol. Endocrinol. 30, 359–368 (2003).
Google Scholar
Lin, K. T. & Wang, L. H. New dimension of glucocorticoids in cancer treatment. Steroids 111, 84–88 (2016).
Google Scholar
Castelo-Branco, G. et al. Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a. Proc. Natl Acad. Sci. USA 100, 12747–12752 (2003).
Google Scholar
Biesecker, L. G. GLI3-Related Pallister–Hall Syndrome in GeneReviews (eds Adam, M. P. et al.) (University of Washington, 2000).
Bose, J., Grotewold, L. & Ruther, U. Pallister–Hall syndrome phenotype in mice mutant for Gli3. Hum. Mol. Genet. 11, 1129–1135 (2002).
Google Scholar
Mandel, H. et al. SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4. Am. J. Hum. Genet. 82, 39–47 (2008).
Google Scholar
Giordano, R. et al. Improvement of anthropometric and metabolic parameters, and quality of life following treatment with dual-release hydrocortisone in patients with Addison’s disease. Endocrine 51, 360–368 (2016).
Google Scholar
Whitaker, M. et al. An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure. Clin. Endocrinol. 80, 554–561 (2014).
Google Scholar
Quinkler, M., Miodini Nilsen, R., Zopf, K., Ventz, M. & Oksnes, M. Modified-release hydrocortisone decreases BMI and HbA1c in patients with primary and secondary adrenal insufficiency. Eur. J. Endocrinol. 172, 619–626 (2015).
Google Scholar
Johannsson, G. et al. Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation. J. Clin. Endocrinol. Metab. 97, 473–481 (2012).
Google Scholar
Graves, L. E. et al. Future directions for adrenal insufficiency: cellular transplantation and genetic therapies. J. Clin. Endocrinol. Metab. 108, 1273–1289 (2023).
Google Scholar
Markmann, S. et al. Biology of the adrenal gland cortex obviates effective use of adeno-associated virus vectors to treat hereditary adrenal disorders. Hum. Gene Ther. 29, 403–412 (2018).
Google Scholar
Tajima, T. et al. Restoration of adrenal steroidogenesis by adenovirus-mediated transfer of human cytochrome P450 21-hydroxylase into the adrenal gland of 21-hydroxylase-deficient mice. Gene Ther. 6, 1898–1903 (1999).
Google Scholar
Onuma, H., Sato, Y. & Harashima, H. Lipid nanoparticle-based ribonucleoprotein delivery for in vivo genome editing. J. Control. Rel. 355, 406–416 (2023).
Google Scholar
Dammes, N. et al. Conformation-sensitive targeting of lipid nanoparticles for RNA therapeutics. Nat. Nanotechnol. 16, 1030–1038 (2021).
Google Scholar
Cruz, L. J., Rezaei, S., Grosveld, F., Philipsen, S. & Eich, C. Nanoparticles targeting hematopoietic stem and progenitor cells: multimodal carriers for the treatment of hematological diseases. Front. Genome Edit. 4, 1030285 (2022).
Google Scholar
Xu, J. et al. Oligodendrocyte progenitor cell-specific delivery of lipid nanoparticles loaded with Olig2 synthetically modified messenger RNA for ischemic stroke therapy. Acta Biomater. 174, 297–313 (2024).
Google Scholar
Tang, Y. et al. Nanoparticle-based RNAi therapeutics targeting cancer stem cells: update and prospective. Pharmaceutics 13, 2116 (2021).
Google Scholar
Ye, C. et al. Overexpression of FZD7 is associated with poor survival in patients with colon cancer. Pathol. Res. Pract. 215, 152478 (2019).
Google Scholar
Zeng, Z. et al. LGR4 overexpression is associated with clinical parameters and poor prognosis of serous ovarian cancer. Cancer Biomark 28, 65–72 (2020).
Google Scholar
Ordaz-Ramos, A., Rosales-Gallegos, V. H., Melendez-Zajgla, J., Maldonado, V. & Vazquez-Santillan, K. The role of LGR4 (GPR48) in normal and cancer processes. Int. J. Mol. Sci. 22, 4690 (2021).
Google Scholar
King, T. D., Zhang, W., Suto, M. J. & Li, Y. Frizzled7 as an emerging target for cancer therapy. Cell Signal. 24, 846–851 (2012).
Google Scholar
Nickho, H. et al. Developing and characterization of single chain variable fragment (scFv) antibody against frizzled 7 (Fzd7) receptor. Bioengineered 8, 501–510 (2017).
Google Scholar
Khodaverdi, E., Shabani, A. A., Madanchi, H. & Farahmand, L. Synthesis of the scFv fragment of anti-Frizzled-7 antibody and evaluation of its effects on triple-negative breast cancer in vitro study. Clin. Transl. Oncol. 26, 231–238 (2024).
Google Scholar
Cao, J. et al. Selective targeting and eradication of LGR5+ cancer stem cells using RSPO-conjugated doxorubicin liposomes. Mol. Cancer Ther. 17, 1475–1485 (2018).
Google Scholar
Graves, L. E. et al. AAV-delivered hepato-adrenal cooperativity in steroidogenesis: implications for gene therapy for congenital adrenal hyperplasia. Mol. Ther. Meth. Clin. Dev. 32, 101232 (2024).
Google Scholar
Balyura, M. et al. Transplantation of bovine adrenocortical cells encapsulated in alginate. Proc. Natl Acad. Sci. USA 112, 2527–2532 (2015).
Google Scholar
Zupekan, T. & Dunn, J. C. Adrenocortical cell transplantation reverses a murine model of adrenal failure. J. Pediat. Surg. 46, 1208–1213 (2011).
Google Scholar
Thomas, M., Wang, X. & Hornsby, P. J. Human adrenocortical cell xenotransplantation: model of cotransplantation of human adrenocortical cells and 3T3 cells in scid mice to form vascularized functional tissue and prevent adrenal insufficiency. Xenotransplantation 9, 58–67 (2002).
Google Scholar
Gondo, S. et al. Adipose tissue-derived and bone marrow-derived mesenchymal cells develop into different lineage of steroidogenic cells by forced expression of steroidogenic factor 1. Endocrinology 149, 4717–4725 (2008).
Google Scholar
Yanase, T. et al. Differentiation and regeneration of adrenal tissues: an initial step toward regeneration therapy for steroid insufficiency. Endocr. J. 53, 449–459 (2006).
Google Scholar
Yazawa, T. et al. Differentiation of adult stem cells derived from bone marrow stroma into Leydig or adrenocortical cells. Endocrinology 147, 4104–4111 (2006).
Google Scholar
Yazawa, T. et al. Differentiation of mesenchymal stem cells and embryonic stem cells into steroidogenic cells using steroidogenic factor-1 and liver receptor homolog-1. Mol. Cell Endocrinol. 336, 127–132 (2011).
Google Scholar
Tanaka, T. et al. Steroidogenic factor 1/adrenal 4 binding protein transforms human bone marrow mesenchymal cells into steroidogenic cells. J. Mol. Endocrinol. 39, 343–350 (2007).
Google Scholar
Gondo, S. et al. SF-1/Ad4BP transforms primary long-term cultured bone marrow cells into ACTH-responsive steroidogenic cells. Genes Cell 9, 1239–1247 (2004).
Google Scholar
Tanaka, T. et al. Extension of survival in bilaterally adrenalectomized mice by implantation of SF-1/Ad4BP-induced steroidogenic cells. Endocrinology 161, bqaa007 (2020).
Google Scholar
Crawford, P. A., Sadovsky, Y. & Milbrandt, J. Nuclear receptor steroidogenic factor 1 directs embryonic stem cells toward the steroidogenic lineage. Mol. Cell Biol. 17, 3997–4006 (1997).
Google Scholar
Oikonomakos, I. et al. In vitro differentiation of mouse pluripotent stem cells into corticosteroid-producing adrenocortical cells. Stem Cell Rep. 19, 1289–1303 (2024).
Google Scholar
Ruiz-Babot, G. et al. Generation of glucocorticoid-producing cells derived from human pluripotent stem cells. Cell Rep. Meth. 3, 100627 (2023).
Google Scholar
Sakata, Y. et al. Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells. Dev. Cell 57, 2566–2583 e2568 (2022).
Google Scholar
Cabrera-Salcedo, C., Kumar, P., Hwa, V. & Dauber, A. IMAGe and related undergrowth syndromes: the complex spectrum of gain-of-function CDKN1C mutations. Pediat. Endocrinol. Rev. 14, 289–297 (2017).
Mathieu, M. et al. Steroidogenic differentiation and PKA signaling are programmed by histone methyltransferase EZH2 in the adrenal cortex. Proc. Natl Acad. Sci. USA 115, E12265–E12274 (2018).
Google Scholar
Pitetti, J. L. et al. Insulin and IGF1 receptors are essential for XX and XY gonadal differentiation and adrenal development in mice. PLoS Genet. 9, e1003160 (2013).
Google Scholar
Suntharalingham, J. P., Buonocore, F., Duncan, A. J. & Achermann, J. C. DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease. Best Pract. Res. Clin. Endocrinol. Metab. 29, 607–619 (2015).
Google Scholar
Luo, X., Ikeda, Y. & Parker, K. L. A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 77, 481–490 (1994).
Google Scholar
Stallings, N. R. et al. Development of a transgenic green fluorescent protein lineage marker for steroidogenic factor 1. Endocr. Res. 28, 497–504 (2002).
Google Scholar
Hobeika, C. et al. Day surgery for acute appendicitis in adults: a prospective series of 102 patients. Surg. Laparosc. Endosc. Percutan. Tech. 27, 158–162 (2017).
Google Scholar
Dufour, D. et al. Loss of SUMO-specific protease 2 causes isolated glucocorticoid deficiency by blocking adrenal cortex zonal transdifferentiation in mice. Nat. Commun. 13, 7858 (2022).
Google Scholar
Maharaj, A. et al. Sphingosine-1-phosphate lyase (SGPL1) deficiency is associated with mitochondrial dysfunction. J. Steroid Biochem. Mol. Biol. 202, 105730 (2020).
Google Scholar
Ching, S. & Vilain, E. Targeted disruption of Sonic Hedgehog in the mouse adrenal leads to adrenocortical hypoplasia. Genesis 47, 628–637 (2009).
Google Scholar
Beuschlein, F. et al. Cortisol producing adrenal adenoma—a new manifestation of Gardner’s syndrome. Endocr. Res. 26, 783–790 (2000).
Google Scholar
Vouillarmet, J. et al. Aldosterone-producing adenoma with a somatic KCNJ5 mutation revealing APC-dependent familial adenomatous polyposis. J. Clin. Endocrinol. Metab. 101, 3874–3878 (2016).
Google Scholar
Gagnon, N. et al. Small adrenal incidentaloma becoming an aggressive adrenocortical carcinoma in a patient carrying a germline APC variant. Endocrine 68, 203–209 (2020).
Google Scholar
Bhandaru, M. et al. Hyperaldosteronism, hypervolemia, and increased blood pressure in mice expressing defective APC. Am. J. Physiol. Regul. Integr. Comp. Physiol 297, R571–R575 (2009).
Google Scholar
Brioude, F. et al. Expert consensus document: clinical and molecular diagnosis, screening and management of Beckwith–Wiedemann syndrome: an international consensus statement. Nat. Rev. Endocrinol. 14, 229–249 (2018).
Google Scholar
Lavoie, J. M. et al. Whole-genome and transcriptome analysis of advanced adrenocortical cancer highlights multiple alterations affecting epigenome and DNA repair pathways. Cold Spring Harb. Mol. Case Stud. 8, a006148 (2022).
Google Scholar
Nazha, B. et al. Blood-based next-generation sequencing in adrenocortical carcinoma. Oncologist 27, 462–468 (2022).
Google Scholar
Zhou, J. et al. Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause. Nat. Genet. 53, 1360–1372 (2021).
Google Scholar
Pignatti, E. et al. β-catenin causes adrenal hyperplasia by blocking zonal transdifferentiation. Cell Rep. 31, 107524 (2020).
Google Scholar
De Martino, M. C. et al. Molecular screening for a personalized treatment approach in advanced adrenocortical cancer. J. Clin. Endocrinol. Metab. 98, 4080–4088 (2013).
Google Scholar
Tamburello, M. et al. FGF/FGFR signaling in adrenocortical development and tumorigenesis: novel potential therapeutic targets in adrenocortical carcinoma. Endocrine 77, 411–418 (2022).
Google Scholar
Pozdeyev, N. et al. Targeted genomic analysis of 364 adrenocortical carcinomas. Endocr. Relat. Cancer 28, 671–681 (2021).
Google Scholar
Almeida, M. Q. et al. Steroidogenic factor 1 overexpression and gene amplification are more frequent in adrenocortical tumors from children than from adults. J. Clin. Endocrinol. Metab. 95, 1458–1462 (2010).
Google Scholar
Cao, Y. et al. Activating hotspot L205R mutation in PRKACA and adrenal Cushing’s syndrome. Science 344, 913–917 (2014).
Google Scholar
Vaduva, P., Bonnet, F. & Bertherat, J. Molecular basis of primary aldosteronism and adrenal Cushing syndrome. J. Endocr. Soc. 4, bvaa075 (2020).
Google Scholar
Perez-Rivas, L. G. et al. TP53 mutations in functional corticotroph tumors are linked to invasion and worse clinical outcome. Acta Neuropathol. Commun. 10, 139 (2022).
Google Scholar
Kratz, C. P. et al. Analysis of the Li–Fraumeni spectrum based on an international germline TP53 variant data set: an international agency for research on cancer TP53 database analysis. JAMA Oncol. 7, 1800–1805 (2021).
Google Scholar
Warde, K. M. et al. Senescence-induced immune remodeling facilitates metastatic adrenal cancer in a sex-dimorphic manner. Nat. Aging 3, 846–865 (2023).
Google Scholar
Del Valle, I. et al. An integrated single-cell analysis of human adrenal cortex development. JCI Insight 8, e168177 (2023).
Google Scholar
Xing, Y., Morohashi, K. I., Ingraham, H. A. & Hammer, G. D. Timing of adrenal regression controlled by synergistic interaction between Sf1 SUMOylation and Dax1. Development 144, 3798–3807 (2017).
Google Scholar
Spencer, S. J., Mesiano, S., Lee, J. Y. & Jaffe, R. B. Proliferation and apoptosis in the human adrenal cortex during the fetal and perinatal periods: implications for growth and remodeling. J. Clin. Endocrinol. Metab. 84, 1110–1115 (1999).
Google Scholar
Niepoth, N. et al. Evolution of a novel adrenal cell type that promotes parental care. Nature 629, 1082–1090 (2024).
Google Scholar
Dumontet, T. et al. Hormonal and spatial control of SUMOylation in the human and mouse adrenal cortex. FASEB J. 33, 10218–10230 (2019).
Google Scholar
Heikkila, M. et al. Wnt-4 deficiency alters mouse adrenal cortex function, reducing aldosterone production. Endocrinology 143, 4358–4365 (2002).
Google Scholar
Leng, S., Carlone, D. L., Guagliardo, N. A., Barrett, P. Q. & Breault, D. T. Rosette morphology in zona glomerulosa formation and function. Mol. Cell Endocrinol. 530, 111287 (2021).
Google Scholar
Leng, S. et al. β-Catenin and FGFR2 regulate postnatal rosette-based adrenocortical morphogenesis. Nat. Commun. 11, 1680 (2020).
Google Scholar
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