Refereed journal article or data article (A1)

Human pluripotent stem cell-derived cells endogenously expressing follicle-stimulating hormone receptors: modeling the function of an inactivating receptor mutation




List of Authors: Lundin K, Sepponen K, Väyrynen P, Liu X, Yohannes DA, Survila M, Ghimire B, Känsäkoski J, Katayama S, Partanen J, Vuoristo S, Paloviita P, Rahman N, Raivio T, Luiro K, Huhtaniemi I, Varjosalo M, Tuuri T, Tapanainen JS

Publisher: OXFORD UNIV PRESS

Publication year: 2022

Journal: Molecular Human Reproduction

Journal name in source: MOLECULAR HUMAN REPRODUCTION

Journal acronym: MOL HUM REPROD

Volume number: 28

Issue number: 5

Number of pages: 13

ISSN: 1360-9947

eISSN: 1460-2407

DOI: http://dx.doi.org/10.1093/molehr/gaac012

URL: https://academic.oup.com/molehr/article/28/5/gaac012/6574364

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/175412513


Abstract
Follicle-stimulating hormone (FSH) is crucial in the development and regulation of reproductive functions. The actions of human FSH and its receptor (FSHR) and mutations therein have mainly been studied using in vivo models, primary cells, cancer cells and cell lines ectopically expressing the FSHR. To allow studies of endogenous FSHR function in vitro, we differentiated FSHR-expressing cells from human pluripotent stem cells. FSH stimulation of the wild-type (WT), but not the inactivating Finnish founder mutant (A189V) receptor, activated the canonical cyclic adenosine monophosphate (cAMP)-dependent signaling pathway and downstream mediators. To investigate protein-protein interaction partners of FSHR at resting state and upon FSH stimulation, we expressed FSHR in HEK293 cells followed by affinity purification mass spectrometry analyses. We found 19 specific high-confidence interacting proteins for WT FSHR and 14 for A189V FSHR, several of which have been linked to infertility. Interestingly, while only WT FSHR interacted with FSH, insulin-like growth factor 1 receptor (IGF1R), for example, interacted with both WT and A189V FSHR upon FSH stimulation. In conclusion, our protocol allows detailed studies of FSH action and disease modeling in human cells endogenously expressing FSHR.

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Last updated on 2022-09-12 at 11:17