Recipe for Pituitary Organoids

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2023 Feb 6

PMID 36743928

Authors

Mayuko Kano

Hiroo Sasaki

Tsutomu Miwata

Hidetaka Suga

Affiliations

Soon will be listed here.

Abstract

Generation of a variety of organs and tissues from human pluripotent stem cells (hPSCs) has been attempted . We here present a simple and efficient method for induction of hypothalamic and pituitary tissues from hPSCs. On provision of exogenous agents important for early hypothalamus-pituitary organogenesis, including bone morphogenetic protein 4 and activators of sonic hedgehog, in three-dimensional culture, hPSCs spontaneously form spherical organoids with two distinct tissues, hypothalamus and adenohypophysis. The pituitary tissues derived from hPSCs not only secrete adenocorticotropic hormone, but also retain both positive and negative feedback mechanisms, recapitulating mature endocrine organs . Furthermore, the results of ectopic transplantation with mouse models of hypopituitarism suggest that these hypothalamus-pituitary organoids have potential as engraftment organs. In addition to their use in transplantation for patients with hypopituitarism they will allow establishment of disease models and enable research impossible in humans. Hypothalamus-pituitary organoids promise to be a powerful tool in regenerative medicine, drug discovery, and basic research into pituitary development.

Citing Articles

Organoid models of the pituitary gland in health and disease.

Laporte E, Vankelecom H Front Endocrinol (Lausanne). 2023; 14:1233714.

PMID: 37614709 PMC: 10442803. DOI: 10.3389/fendo.2023.1233714.

References

Dincer Z, Piao J, Niu L, Ganat Y, Kriks S, Zimmer B . Specification of functional cranial placode derivatives from human pluripotent stem cells. Cell Rep. 2013; 5(5):1387-402. PMC: 3887225. DOI: 10.1016/j.celrep.2013.10.048. View

Zimmer B, Piao J, Ramnarine K, Tomishima M, Tabar V, Studer L . Derivation of Diverse Hormone-Releasing Pituitary Cells from Human Pluripotent Stem Cells. Stem Cell Reports. 2016; 6(6):858-872. PMC: 4912387. DOI: 10.1016/j.stemcr.2016.05.005. View

Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D . High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2014; 100(2):407-16. DOI: 10.1210/jc.2014-3191. View

Watanabe K, Kamiya D, Nishiyama A, Katayama T, Nozaki S, Kawasaki H . Directed differentiation of telencephalic precursors from embryonic stem cells. Nat Neurosci. 2005; 8(3):288-96. DOI: 10.1038/nn1402. View

Suga H, Kadoshima T, Minaguchi M, Ohgushi M, Soen M, Nakano T . Self-formation of functional adenohypophysis in three-dimensional culture. Nature. 2011; 480(7375):57-62. DOI: 10.1038/nature10637. View

Wataya T, Ando S, Muguruma K, Ikeda H, Watanabe K, Eiraku M . Minimization of exogenous signals in ES cell culture induces rostral hypothalamic differentiation. Proc Natl Acad Sci U S A. 2008; 105(33):11796-801. PMC: 2575295. DOI: 10.1073/pnas.0803078105. View

Kasai T, Suga H, Sakakibara M, Ozone C, Matsumoto R, Kano M . Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells. Cell Rep. 2020; 30(1):18-24.e5. DOI: 10.1016/j.celrep.2019.12.009. View

Kawabata T, Suga H, Takeuchi K, Nagata Y, Sakakibara M, Ushida K . A new primate model of hypophyseal dysfunction. Sci Rep. 2021; 11(1):10729. PMC: 8144576. DOI: 10.1038/s41598-021-90209-3. View

Ngaosuwan K, Johnston D, Godsland I, Cox J, Majeed A, Quint J . Increased Mortality Risk in Patients With Primary and Secondary Adrenal Insufficiency. J Clin Endocrinol Metab. 2021; 106(7):e2759-e2768. DOI: 10.1210/clinem/dgab096. View

10.

Nakano T, Ando S, Takata N, Kawada M, Muguruma K, Sekiguchi K . Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell. 2012; 10(6):771-785. DOI: 10.1016/j.stem.2012.05.009. View

11.

Matsumoto R, Suga H, Aoi T, Bando H, Fukuoka H, Iguchi G . Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells. J Clin Invest. 2019; 130(2):641-654. PMC: 6994153. DOI: 10.1172/JCI127378. View

12.

Miyake N, Nagai T, Suga H, Osuka S, Kasai T, Sakakibara M . Functional Lactotrophs in Induced Adenohypophysis Differentiated From Human iPS Cells. Endocrinology. 2022; 163(3). DOI: 10.1210/endocr/bqac004. View

13.

Park B, Saint-Jeannet J . Hindbrain-derived Wnt and Fgf signals cooperate to specify the otic placode in Xenopus. Dev Biol. 2008; 324(1):108-21. PMC: 2605947. DOI: 10.1016/j.ydbio.2008.09.009. View

14.

Scully K, Rosenfeld M . Pituitary development: regulatory codes in mammalian organogenesis. Science. 2002; 295(5563):2231-5. DOI: 10.1126/science.1062736. View

15.

Ozone C, Suga H, Eiraku M, Kadoshima T, Yonemura S, Takata N . Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells. Nat Commun. 2016; 7:10351. PMC: 4735598. DOI: 10.1038/ncomms10351. View

16.

Matsumoto R, Suga H, Arima H, Yamamoto T . Disease Modeling of Pituitary Adenoma Using Human Pluripotent Stem Cells. Cancers (Basel). 2022; 14(15). PMC: 9367606. DOI: 10.3390/cancers14153660. View