Generation of blastoids from human parthenogenetic stem cells

Ke Zhong, Yu-Xin Luo, Dan Li, Zhe-Ying Min, Yong Fan, Yang Yu

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Life Medicine ›› 2023, Vol. 2 ›› Issue (1) : 8. DOI: 10.1093/lifemedi/lnad006
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Article

Generation of blastoids from human parthenogenetic stem cells

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Abstract

Parthenogenetic embryos derive their genomes entirely from the maternal genome and lack paternal imprint patterns. Many achievements have been made in the study of genomic imprinting using human parthenogenetic embryonic stem cells (hPg-ESCs). However, due to developmental defects and ethical limits, a comprehensive understanding of parthenogenetic embryonic development is still lacking. Here, we generated parthenogenetic blastoids (hPg-EPSCs blastoids) from hPg-ESC-derived extended pluripotent stem cells (hPg-EPSCs) using our previously published two-step induction protocol. Morphology, specific marker expression and single-cell transcriptome analysis showed that hPg-EPSCs blastoids contain crucial cell lineages similar to blastoids (hBp-EPSCs blastoids) generated from human biparental EPSCs (hBp-EPSCs). Single-cell RNA-seq compared the expression of genes related to imprinting and X chromosome inactivation in hPg-EPSCs blastoids and hBp-EPSCs blastoids. In conclusion, we generated parthenogenetic blastoids, which will potentially promote the study of genomic imprinting in embryonic development and uncover the influence of parental origin bias on human development and pathological mechanisms.

Keywords

human parthenogenetic ESCs / blastoids / hEPSCs / imprinted genes / X chromosome

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Ke Zhong, Yu-Xin Luo, Dan Li, Zhe-Ying Min, Yong Fan, Yang Yu. Generation of blastoids from human parthenogenetic stem cells. Life Medicine, 2023, 2(1): 8 https://doi.org/10.1093/lifemedi/lnad006

References

[1]
Brevini TA, Gandolfi F. Parthenotes as a source of embryonic stem cells. Cell Prolif 2008;41:20–30.
CrossRef Google scholar
[2]
Surani MA, Barton SC, Norris ML. Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis, Nature 1984;308:548–50.
CrossRef Google scholar
[3]
Linder D, McCaw BK, Hecht F. Parthenogenic origin of benign ovarian teratomas. N Engl J Med 1975;292:63–6.
CrossRef Google scholar
[4]
Kim K, Lerou P, Yabuuchi A, et al. Histocompatible embryonic stem cells by parthenogenesis. Science 2007;315:482–6.
CrossRef Google scholar
[5]
Mai Q, Yu Y, Li T, et al. Derivation of human embryonic stem cell lines from parthenogenetic blastocysts. Cell Res 2007;17:1008–19.
CrossRef Google scholar
[6]
Revazova ES, Turovets NA, Kochetkova OD, et al. Patient-specific stem cell lines derived from human parthenogenetic blastocysts. Cloning Stem Cells 2007;9:432–49.
CrossRef Google scholar
[7]
Yu Y, Gao Q, Zhao H-C, et al. Ascorbic acid improves pluripotency of human parthenogenetic embryonic stem cells through modifying imprinted gene expression in the Dlk1-Dio3 region. Stem Cell Res Ther 2015;6:69.
CrossRef Google scholar
[8]
Thomson JA, Solter D. The developmental fate of androgenetic, parthenogenetic, and gynogenetic cells in chimeric gastrulating mouse embryos. Genes Dev 1988;2:1344–51.
CrossRef Google scholar
[9]
Barton SC, Surani MA, Norris ML. Role of paternal and maternal genomes in mouse development. Nature 1984;311:374–6.
CrossRef Google scholar
[10]
Tucci V, Isles AR, Kelsey G, et al; Erice Imprinting Group. Genomic imprinting and physiological processes in mammals. Cell 2019;176:952–65.
CrossRef Google scholar
[11]
Sagi, I, De Pinho Joao C, Zuccaro MV, et al. Distinct imprinting signatures and biased differentiation of human androgenetic and parthenogenetic embryonic stem cells, Cell Stem Cell, 2019;25:419–432.e9.
CrossRef Google scholar
[12]
Fan Y, Min Z, Alsolami S, et al. Generation of human blastocyst-like structures from pluripotent stem cells. Cell Discov 2021;7:81.
CrossRef Google scholar
[13]
Kagawa H, Javali A, Khoei HH, et al. Human blastoids model blastocyst development and implantation. Nature 2022;601:600–5.
CrossRef Google scholar
[14]
Liu XD et al. Modelling human blastocysts by reprogramming fibroblasts into iBlastoids. Nature 2021;591:627.
CrossRef Google scholar
[15]
Sozen B, Jorgensen V, Weatherbee BAT, et al. Reconstructing aspects of human embryogenesis with pluripotent stem cells. Nat Commun 2021;12:5550.
CrossRef Google scholar
[16]
Yanagida, A, Spindlow D, Nichols J, et al. Naive stem cell blastocyst model captures human embryo lineage segregation, Cell Stem Cell 2021;28:1016–1022.e4.
CrossRef Google scholar
[17]
Yu L, Wei Y, Duan J, et al. Blastocyst-like structures generated from human pluripotent stem cells. Nature 2021;591:620–6.
CrossRef Google scholar
[18]
Li T, Vu TH, Lee K-O, et al. An imprinted PEG1/MEST antisense expressed predominantly in human testis and in mature spermatozoa. J Biol Chem 2002;277:13518–27.
CrossRef Google scholar
[19]
Io, S, Kabata M, Iemura Y, et al. Capturing human trophoblast development with naive pluripotent stem cells in vitro, Cell Stem Cell 2021;28:1023–39.e13.
CrossRef Google scholar
[20]
Qi Q, Ding C, Hong P, et al. X chromosome inactivation in human parthenogenetic embryonic stem cells following prolonged passaging. Int J Mol Med 2015;35:569–78.
CrossRef Google scholar
[21]
Moreira de Mello JC, Fernandes GR, Vibranovski MD, et al. Early X chromosome inactivation during human preimplantation development revealed by single-cell RNA-sequencing. Sci Rep 2017;7:10794.
CrossRef Google scholar
[22]
Patrat C, Ouimette JF, Rougeulle C. X chromosome inactivation in human development, Development 2020;147:dev183095.
CrossRef Google scholar
[23]
Sun S, Del Rosario BC, Szanto A, et al. Jpx RNA activates Xist by evicting CTCF. Cell 2013;153:1537–51.
CrossRef Google scholar
[24]
Tian, D, Sun, S, Lee, JT. The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell 2010;143:390–403.
CrossRef Google scholar
[25]
Furlan G, Gutierrez Hernandez N, Huret C, et al. The ftx noncoding locus controls X chromosome inactivation independently of Its RNA products. Mol Cell 2018;70:462–472.e8.
CrossRef Google scholar
[26]
Nora EP, Lajoie BR, Schulz EG, et al. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 2012;485:381–5.
CrossRef Google scholar
[27]
Rosspopoff O, Huret C, Collier AJ, et al. Mechanistic diversification of XIST regulatory network in mammals. bioRxiv 2019;689430.
CrossRef Google scholar
[28]
Pastor WA, Chen D, Liu W, et al. Naive human pluripotent cells feature a methylation landscape devoid of blastocyst or germline memory. Cell Stem Cell 2016;18:323–9.
CrossRef Google scholar
[29]
Pereira G, Doria S. X-chromosome inactivation: implications in human disease. J Genet 2021;100:63.
CrossRef Google scholar
[30]
Okamoto I, Patrat C, Thépot D, et al. Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development. Nature 2011;472:370–4.
CrossRef Google scholar
[31]
Petropoulos S, Edsgärd D, Reinius B, et al. Single-cell RNA-seq reveals lineage and X chromosome dynamics in human preimplantation embryos. Cell 2016;167:285.
CrossRef Google scholar
[32]
Vallot C, Patrat C, Collier AJ, et al. XACT Noncoding RNA competes with XIST in the control of X chromosome activity during human early development. Cell Stem Cell 2017;20:102–11.
CrossRef Google scholar
[33]
Zhou Q, Wang T, Leng L, et al. Single-cell RNA-seq reveals distinct dynamic behavior of sex chromosomes during early human embryogenesis. Mol Reprod Dev 2019;86:871–82.
CrossRef Google scholar
[34]
Skakkebaek A, Bojesen A, Kristensen MK, et al. Neuropsychology and brain morphology in Klinefelter syndrome - the impact of genetics. Andrology 2014;2:632–40.
CrossRef Google scholar
[35]
Okamoto I, Otte AP, Allis CD, et al. Epigenetic dynamics of imprinted X inactivation during early mouse development. Science 2004;303:644–9.
CrossRef Google scholar
[36]
Moreira de Mello JC, de Araújo ESS, Stabellini R, et al. Random X inactivation and extensive mosaicism in human placenta revealed by analysis of allele-specific gene expression along the X chromosome. PLoS One 2010;5:e10947.
CrossRef Google scholar
[37]
Hamada H, Okae H, Toh H, et al. Allele-specific methylome and transcriptome analysis reveals widespread imprinting in the human placenta. Am J Hum Genet 2016;99:1045–58.
CrossRef Google scholar

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2023 The Author(s) 2023. Published by Oxford University Press on behalf of Higher Education Press.
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