On October 3, the CSU (short for Central South University) research team led by Lin Ge, the CAMS (short for China Academy of Medical Sciences) research team led by Jiang Taijiao , and the BGI-Shenzhen (short for BGI Life Science Research Institution) research team led by Xu Fengping published onCell Stem Cell(IF: 21.46) online their latest research findings - "Single-cell transcriptome analysis of uniparental embryos reveals parent-of-origin effects on human preimplantation development".. This study has firstly profiled the transcriptomes and DNA methylation map for preimplantation development stage of human biparental and uniparental embryos. In the study, 1388 parental genomes specific genes were identified and the role of parental genomes in preimplantation embryonic genome activation (EGA) and cell differentiation was clarified. Dr. Leng Lizhi from CSU, Dr. Sun Jiya from CAMS and Dr. Huang Jinrong from BGI-Shenzhen are co-first authors. Professor Lin Ge from CSU, Dr. Xu Fengping from BGI-Shenzhen and Professor Jiang Taijiao from CAMS are the co-corresponding author, and CSU is the first unit and the first corresponding unit.
(summarize the influence of parental genomes on early embryo development)
Thein vitroblastocyst formation rate of human fertilized embryos is relatively low with the development mostly blocked at the 4-8-cell stage due to unknown reasons. To solve this clinical problem, the Lin Ge research team and its cooperating teams systematically studied the effects of parental genomes on early embryo development, based on models of parthenogenetic (PG), androgenetic (AG) and normal fertilized embryos (BI), using embryonic time-lapse imaging and single-cell transcriptome sequencing technology. The study found that compared with the biparental embryos, the uniparental embryos exhibited a lower developmental potential and a higher frequency of abnormal cleavage behavior; besides, the developmental speeds of uniparental and biparental embryos were significantly different, and while AG developed faster and PG developed slow relatively. On this ground, the teams further cultured three groups of embryos into blastocysts. As observed, BI can form a large blastocyst cavity, and an outer smooth trophectoderm (TE) and clearly visible inner cell mass (ICM) can be seen in the cavity; conversely, AG and PG blastocysts displayed major differentiation defects with no viable ICMs in AG blastocysts and only limited TE development in PG blastocysts. Meanwhile, the teams subjected the fertilized embryos of the three group to single-cell transcriptome sequencing. The results showed that the main EGAs of the three groups of embryos occurred from 4-cell to morula stage, but uniparental embryos showed decreased EGA activation and incomplete maternal substances clearance. The comparative transcriptome analysis of biparental and uniparental embryos identified 807 maternally biased expressed genes (MBGs) and 581 paternally biased expressed genes (PBGs). The MBGs started to express at the 4-cell stage, which is an important contribution to the initiation of the EGA process. PBGs tend to begin to express at the 8-cell stage, which closely related to embryo compaction and TE differentiation, thus confirming the phenotypic differences between biparental and uniparental embryos.
In order to further reveal the regulation mechanism of MBGs and PBGs in human preimplantation embryos, the teams conducted a transcription factor regulatory network analysis for MBGs and PBGs, revealing that DUX4, EGR2, and DUXA are key transcription factors in MBGs’expression and that ZNF263 and KLF3 are important for PBGs’expression. In addition, the teams also analyzed the DNA methylation status of MBGs and PBGs in the three groups of embryos, and found that the expression of PBGs is closely related to the parent-specific DNA methylation pattern. The research comprehensively maps the parental genome regulatory network of early embryo development, which has great value for understanding early embryo development and regulation mechanism, and provides a new theoretical basis for the diagnosis and treatment of intractable clinical cases such as embryo development abnormalities.
Professor Lin Ge's team has been devoted to the early embryo development basic research for application in recent years. Previously (in January this year), their research results related to the chromatin changes and gene transcription of human preimplantation embryos were published by the leading international academic journal “Nature Communication” (IF=12.19). The results have for the first time systematically depicted the dynamic changes in chromatin status and gene expression during key stages of early human embryo development on the level of chromatin opening and transcription.
The research was supported by several projects including the National Natural Science Foundation of China (NSFC) and the National Key Research and Development Program of China (NKP).
Source: School of Basic Medicine