The Establishment of Human Embryonic Stem Cell Lines Demonstrated that Mosaic Embryos Have the Potential of Self-Correction

Chuyu Li, Xiaohan Dong, Jiazi Xie, Juan Dong, Chao Gao, Meng Xia, Yuting Lin, Yugui Cui, Lianju Qin, Wei Wu

Article ID: 7790
Vol 38, Issue 1, 2024
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20243801.61
Received: 20 January 2024; Accepted: 20 January 2024; Available online: 20 January 2024; Issue release: 20 January 2024

Abstract

Background: Low-level mosaicism is a common trait of early human development. Although mosaic embryos may lead to healthy live births, the direct effects of mosaicism are unknown. While embryo self-correction was demonstrated in mouse models, humans can only study the effects of chromosomal aberrations and blastocyst mosaicism on the early peri-implantation period by extending in vitro embryo culture up to 12 days post-fertilization. Methods: The established culture protocols were followed to generate embryonic stem cells. The 24 high-quality mosaicism/aneuploid mosaicism blastocysts were detected by preimplantation genetic testing for aneuploidy (PGT-A). The isolated inner cell masses (ICMs) were seeded onto feeder-free dishes, and after 10–12 days of culture, there were six blastocyst ICM-generated stem cell clones. The cells shed during the stem cell growth were harvested, and next-generation sequencing was performed on stem cells and the shed cells. To test pluripotency, a small number of stem cells were isolated and subcultured. Results: The PGT-A status was confirmed from the results of next-generation sequencing of stem cell exfoliated cells and stem cells. The mosaics in five blastocysts were fully repaired while the mosaic in one blastocyst was partially repaired. Simultaneously, the cells were verified to have pluripotency and the ability to differentiate into three germ layers by immunofluorescence, flow cytometry, and in vitro differentiation analyses. Conclusion: Human mosaicism/aneuploid mosaicism blastocysts have the potential for self-correction by eliminating mosaic cells.


Keywords

human blastocyst;mosaic;stem cells;cell debris;self-correction


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