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Generation of developmentally competent oocytes and fertile mice from parthenogenetic embryonic stem cells
Parthenogenetic embryos, created by activation and diploidization of oocytes, arrest at mid-gestation for defective paternal imprints, which impair placental development. Also, viable offspring has not been obtained without genetic manipulation from parthenogenetic embryonic stem cells (pESCs) deriv...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Higher Education Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674391/ https://www.ncbi.nlm.nih.gov/pubmed/34845589 http://dx.doi.org/10.1007/s13238-021-00865-4 |
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author | Tian, Chenglei Liu, Linlin Zeng, Ming Sheng, Xiaoyan Heng, Dai Wang, Lingling Ye, Xiaoying Keefe, David L. Liu, Lin |
author_facet | Tian, Chenglei Liu, Linlin Zeng, Ming Sheng, Xiaoyan Heng, Dai Wang, Lingling Ye, Xiaoying Keefe, David L. Liu, Lin |
author_sort | Tian, Chenglei |
collection | PubMed |
description | Parthenogenetic embryos, created by activation and diploidization of oocytes, arrest at mid-gestation for defective paternal imprints, which impair placental development. Also, viable offspring has not been obtained without genetic manipulation from parthenogenetic embryonic stem cells (pESCs) derived from parthenogenetic embryos, presumably attributable to their aberrant imprinting. We show that an unlimited number of oocytes can be derived from pESCs and produce healthy offspring. Moreover, normal expression of imprinted genes is found in the germ cells and the mice. pESCs exhibited imprinting consistent with exclusively maternal lineage, and higher X-chromosome activation compared to female ESCs derived from the same mouse genetic background. pESCs differentiated into primordial germ cell-like cells (PGCLCs) and formed oocytes following in vivo transplantation into kidney capsule that produced fertile pups and reconstituted ovarian endocrine function. The transcriptome and methylation of imprinted and X-linked genes in pESC-PGCLCs closely resembled those of in vivo produced PGCs, consistent with efficient reprogramming of methylation and genomic imprinting. These results demonstrate that amplification of germ cells through parthenogenesis faithfully maintains maternal imprinting, offering a promising route for deriving functional oocytes and having potential in rebuilding ovarian endocrine function. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13238-021-00865-4. |
format | Online Article Text |
id | pubmed-8674391 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Higher Education Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-86743912021-12-17 Generation of developmentally competent oocytes and fertile mice from parthenogenetic embryonic stem cells Tian, Chenglei Liu, Linlin Zeng, Ming Sheng, Xiaoyan Heng, Dai Wang, Lingling Ye, Xiaoying Keefe, David L. Liu, Lin Protein Cell Research Article Parthenogenetic embryos, created by activation and diploidization of oocytes, arrest at mid-gestation for defective paternal imprints, which impair placental development. Also, viable offspring has not been obtained without genetic manipulation from parthenogenetic embryonic stem cells (pESCs) derived from parthenogenetic embryos, presumably attributable to their aberrant imprinting. We show that an unlimited number of oocytes can be derived from pESCs and produce healthy offspring. Moreover, normal expression of imprinted genes is found in the germ cells and the mice. pESCs exhibited imprinting consistent with exclusively maternal lineage, and higher X-chromosome activation compared to female ESCs derived from the same mouse genetic background. pESCs differentiated into primordial germ cell-like cells (PGCLCs) and formed oocytes following in vivo transplantation into kidney capsule that produced fertile pups and reconstituted ovarian endocrine function. The transcriptome and methylation of imprinted and X-linked genes in pESC-PGCLCs closely resembled those of in vivo produced PGCs, consistent with efficient reprogramming of methylation and genomic imprinting. These results demonstrate that amplification of germ cells through parthenogenesis faithfully maintains maternal imprinting, offering a promising route for deriving functional oocytes and having potential in rebuilding ovarian endocrine function. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13238-021-00865-4. Higher Education Press 2021-11-30 2021-12 /pmc/articles/PMC8674391/ /pubmed/34845589 http://dx.doi.org/10.1007/s13238-021-00865-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Tian, Chenglei Liu, Linlin Zeng, Ming Sheng, Xiaoyan Heng, Dai Wang, Lingling Ye, Xiaoying Keefe, David L. Liu, Lin Generation of developmentally competent oocytes and fertile mice from parthenogenetic embryonic stem cells |
title | Generation of developmentally competent oocytes and fertile mice from parthenogenetic embryonic stem cells |
title_full | Generation of developmentally competent oocytes and fertile mice from parthenogenetic embryonic stem cells |
title_fullStr | Generation of developmentally competent oocytes and fertile mice from parthenogenetic embryonic stem cells |
title_full_unstemmed | Generation of developmentally competent oocytes and fertile mice from parthenogenetic embryonic stem cells |
title_short | Generation of developmentally competent oocytes and fertile mice from parthenogenetic embryonic stem cells |
title_sort | generation of developmentally competent oocytes and fertile mice from parthenogenetic embryonic stem cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674391/ https://www.ncbi.nlm.nih.gov/pubmed/34845589 http://dx.doi.org/10.1007/s13238-021-00865-4 |
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