NANOS3 Downregulation in Down Syndrome HiPSCs During Primordial Germ Cell-like Cell Differentiation

Overview

Journal Histochem Cell Biol

Publisher Springer

Specialties Biochemistry
Cell Biology

Date 2021 Oct 15

PMID 34652540

Citations 1

Authors

V K Abdyyev

N O Dashenkova

E B Dashinimaev

E A Vorotelyak

a V Vasiliev

Affiliations

Soon will be listed here.

Abstract

Human infertility is a complex disorder at the genetic, molecular, cellular, organ, and hormonal levels. New developing technology based on the generation of human primordial germ cell-like cells (hPGCLCs) from induced pluripotent stem cells (hiPSCs) might improve understanding of early germ cell development (specification, migration, gametogenesis, and epigenetic reconstitutions), as well as offering a solution for infertility and hereditary disorders. In this study, we differentiated hiPSCs with trisomy 21 into hPGCLCs. In vitro-derived germ cells from hiPSCs with Down syndrome (DS) express hPGCLC core circuitry, EOMES, SOX17, and PRDM14 at relatively low levels. TFAP2C and PRDM1 were expressed and remained elevated, whereas NANOS3 and NANOG were downregulated in BMP4-induced hiPSCs with DS. The low level of NANOG and NANOS3 expression might negatively influence hPGCLC generation in DS hiPSCs. We suggest that DS hPGCLCs could be a suitable model for studying human early germ cell development, the epigenetic and molecular mechanisms of PGC specification and formation, as well as related infertility disorders, such as azoospermia and teratozoospermia.

Citing Articles

In focus in HCB.

Taatjes D, Roth J Histochem Cell Biol. 2022; 157(1):1-5.

PMID: 34981200 DOI: 10.1007/s00418-021-02064-y.

References

Abdyyev V, Sant D, Kiseleva E, Spangenberg V, Kolomiets O, Andrade N . In vitro derived female hPGCLCs are unable to complete meiosis in embryoid bodies. Exp Cell Res. 2020; 397(2):112358. DOI: 10.1016/j.yexcr.2020.112358. View

Chew G, Hutson J . Incidence of cryptorchidism and ascending testes in trisomy 21: a 10 year retrospective review. Pediatr Surg Int. 2004; 20(10):744-7. DOI: 10.1007/s00383-004-1290-8. View

Deshpande G, Calhoun G, Yanowitz J, Schedl P . Novel functions of nanos in downregulating mitosis and transcription during the development of the Drosophila germline. Cell. 1999; 99(3):271-81. DOI: 10.1016/s0092-8674(00)81658-x. View

Deutsch S, Lyle R, Dermitzakis E, Attar H, Subrahmanyan L, Gehrig C . Gene expression variation and expression quantitative trait mapping of human chromosome 21 genes. Hum Mol Genet. 2005; 14(23):3741-9. DOI: 10.1093/hmg/ddi404. View

EYMAN R, Call T . Life expectancy of persons with Down syndrome. Am J Ment Retard. 1991; 95(6):603-12. View

Goday C, Pimpinelli S . The occurrence, role and evolution of chromatin diminution in nematodes. Parasitol Today. 1993; 9(9):319-22. DOI: 10.1016/0169-4758(93)90229-9. View

Hsiang Y, Berkovitz G, Bland G, Migeon C, Warren A . Gonadal function in patients with Down syndrome. Am J Med Genet. 1987; 27(2):449-58. DOI: 10.1002/ajmg.1320270223. View

Jazayeri O, Gorjizadeh N . A male Down syndrome with two normal boys: Cytogenetic, paternity and andrological investigations. Andrologia. 2020; 52(3):e13521. DOI: 10.1111/and.13521. View

Kuliev A, Verlinsky Y . Meiotic and mitotic nondisjunction: lessons from preimplantation genetic diagnosis. Hum Reprod Update. 2004; 10(5):401-7. DOI: 10.1093/humupd/dmh036. View

10.

Liu X, Nefzger C, Rossello F, Chen J, Knaupp A, Firas J . Comprehensive characterization of distinct states of human naive pluripotency generated by reprogramming. Nat Methods. 2017; 14(11):1055-1062. DOI: 10.1038/nmeth.4436. View

11.

Miki M, Ohtake N, Hasumi M, Ohi M, Moriyama S . Seminoma associated with bilateral cryptorchidism in Down's syndrome: a case report. Int J Urol. 1999; 6(7):377-80. DOI: 10.1046/j.1442-2042.1999.00078.x. View

12.

Muller F, Tobler H . Chromatin diminution in the parasitic nematodes ascaris suum and parascaris univalens. Int J Parasitol. 2000; 30(4):391-9. DOI: 10.1016/s0020-7519(99)00199-x. View

13.

Muller F, Bernard V, Tobler H . Chromatin diminution in nematodes. Bioessays. 1996; 18(2):133-8. DOI: 10.1002/bies.950180209. View

14.

Panula S, Reda A, Stukenborg J, Ramathal C, Sukhwani M, Albalushi H . Over Expression of NANOS3 and DAZL in Human Embryonic Stem Cells. PLoS One. 2016; 11(10):e0165268. PMC: 5074499. DOI: 10.1371/journal.pone.0165268. View

15.

Papavassiliou P, Charalsawadi C, Rafferty K, Jackson-Cook C . Mosaicism for trisomy 21: a review. Am J Med Genet A. 2014; 167A(1):26-39. DOI: 10.1002/ajmg.a.36861. View

16.

Perrett R, Turnpenny L, Eckert J, OShea M, Sonne S, Cameron I . The early human germ cell lineage does not express SOX2 during in vivo development or upon in vitro culture. Biol Reprod. 2008; 78(5):852-8. DOI: 10.1095/biolreprod.107.066175. View

17.

Prandini P, Deutsch S, Lyle R, Gagnebin M, Delucinge Vivier C, Delorenzi M . Natural gene-expression variation in Down syndrome modulates the outcome of gene-dosage imbalance. Am J Hum Genet. 2007; 81(2):252-63. PMC: 1950802. DOI: 10.1086/519248. View

18.

Sugawa F, Arauzo-Bravo M, Yoon J, Kim K, Aramaki S, Wu G . Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile. EMBO J. 2015; 34(8):1009-24. PMC: 4406649. DOI: 10.15252/embj.201488049. View

19.

Sybirna A, Tang W, Pierson Smela M, Dietmann S, Gruhn W, Brosh R . A critical role of PRDM14 in human primordial germ cell fate revealed by inducible degrons. Nat Commun. 2020; 11(1):1282. PMC: 7062732. DOI: 10.1038/s41467-020-15042-0. View

20.

Welling M, Chen H, Munoz J, Musheev M, Kester L, Junker J . DAZL regulates Tet1 translation in murine embryonic stem cells. EMBO Rep. 2015; 16(7):791-802. PMC: 4515119. DOI: 10.15252/embr.201540538. View