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Temporal regulation of prenatal embryonic development by paternal imprinted loci

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Abstract

Paternal imprinted genes (H19 and Gtl2) are pivotal for prenatal embryonic development in mice. Nongrowing oocytes and sperm- or oocyte-originated haploid embryonic stem cells (haESCs) carrying both H19-DMR (differentially DNA-methylated region) and IG (intergenic)-DMR deletions that partially mimic paternal imprinting of H19-Igf2 and Dlk1-Dio3 can be employed as sperm replacement to efficiently support full-term embryonic development. However, how H19-DMR and IG-DMR act together to regulate embryonic development is still largely unknown. Here, using androgenetic haESC (AG-haESC)-mediated semi-cloned (SC) technology, we showed that paternal H19-DMR and IG-DMR are not essential for pre-implantation development of SC embryos generated through injection of AG-haESCs into oocytes. H19-DMR plays critical roles before 12.5 days of gestation while IG-DMR is essential for late-gestation of SC embryos. Interestingly, we found that combined deletions of H19 and H19-DMR can further improve the efficiency of normal development of SC embryos at mid-gestation compared to DKO SC embryos. Transcriptome and histology analyses revealed that H19 and H19-DMR combined deletions rescue the placental defects. Furthermore, we showed that H19, H19-DMR and IG-DMR deletions (TKO) give rise to better prenatal and postnatal embryonic development of SC embryos compared to DKO. Together, our results indicate the temporal regulation of paternal imprinted loci during embryonic development.

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Data availability

The RNA sequencing data of blastocysts and placentas from this study have been deposited in the Gene Expression Omnibus (GEO) under accession number GSE132254. The RNA sequencing data of AGH-OG3 and H19ΔDMR-IGΔDMRAGH-OG3 obtained from our previous work under the accession number GSE60072. The RNA sequencing data of ICM and TE of E3.5 and Epi and VE of E6.5 from previous work under the accession number GSE76505. All other data supporting the findings of this study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was partly supported by the Genome Tagging Project, Fountain-Valley Life Sciences Fund of University of Chinese Academy of Sciences Education Foundation and grants from the Chinese Academy of Sciences (XDB19010204, OYZDJ-SSW-SMC023 and Facility-based Open Research Program), the National Natural Science Foundation of China (31530048, 81672117, 31730062, 31821004, and 31601163), the Ministry of Science and Technology of China (2019YFA0109900), and Shanghai Municipal Commission for Science and Technology (16JC1420500, 17JC1420102, 17JC1400900, and 17411954900).

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Authors and Affiliations

  1. State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China

    Qing Li, Yuanyuan Li, Qi Yin, Kai Wang, Wei Li, Boran Chang & Jinsong Li

  2. School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China

    Shuo Huang, Liangchai Zhuo & Jinsong Li

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  1. Qing Li
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  2. Yuanyuan Li
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Correspondence to Jinsong Li.

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Li, Q., Li, Y., Yin, Q. et al. Temporal regulation of prenatal embryonic development by paternal imprinted loci. Sci. China Life Sci. 63, 1–17 (2020). https://doi.org/10.1007/s11427-019-9817-6

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