The Dynamic Changes of Transcription Factors During the Development Processes of Human Biparental and Uniparental Embryos.

Chenxi Zhang,Fengping Xu,Conghui Li,Jinrong Huang,Lars Bolund,Xuemei Li,Guibo Li,Depeng Zhao,Ge Lin,Fang Fang,Lizhi Leng,Dragomirka Jovic,Ling Yang,Yonglun Luo,Lin Lin,Jun Wang

doi:10.3389/fcell.2021.709498

Abstract

Previous studies have revealed that transcription factors (TFs) play important roles in biparental (BI) early human embryogenesis. However, the contribution of TFs during early uniparental embryo development is still largely unknown. Here we systematically studied the expression profiles of transcription factors in early embryonic development and revealed the dynamic changes of TFs in human biparental and uniparental embryogenesis by single-cell RNA sequencing (scRNA-seq). In general, the TF expression model of uniparental embryos showed a high degree of conformity with biparental embryos. The detailed network analysis of three different types of embryos identified that 10 out of 17 hub TFs were shared or specifically owned, such as ZNF480, ZNF581, PHB, and POU5F1, were four shared TFs, ZFN534, GTF3A, ZNF771, TEAD4, and LIN28A, were androgenic (AG) specific TFs, and ZFP42 was the only one parthenogenetic (PG) specific TF. All the four shared TFs were validated using human embryonic stem cell (hESC) differentiation experiments; most of their target genes are responsible for stem cell maintenance and differentiation. We also found that Zf-C2H2, HMG, and MYB were three dominant transcription factor families that appeared in early embryogenesis. Altogether, our work provides a comprehensive regulatory framework and better understanding of TF function in human biparental and uniparental embryogenesis.

Highlights

Transcription factors (TFs) are essential for the regulation of gene expression (Thomas et al, 2010); numerous transcription factors in multicellular organisms are capable of regulating the genes involved in development and functions (Marsman and Horsfield, 2012), which control crucial cellular processes like apoptosis, cell growth, and cellular differentiation
From previous reports (Niakan and Eggan, 2013; Godini and Fallahi, 2019), TFs have important functions in initial embryonic genome activation (EGA), which involved dramatic expression changes during preimplantation development; we explored the different contributions of TFs in biparental and uniparental embryonic development
We further explored the contribution of TFs to the biological processes and key events in these five early stages in both uniparental and biparental embryos

Summary

Introduction

Transcription factors (TFs) are essential for the regulation of gene expression (Thomas et al, 2010); numerous transcription factors in multicellular organisms are capable of regulating the genes involved in development and functions (Marsman and Horsfield, 2012), which control crucial cellular processes like apoptosis, cell growth, and cellular differentiation. Previous studies have revealed that TFs play important roles in biparental early embryogenesis, for instance, Foxo, Foxo, and Foxo are differently expressed during mouse oocyte maturation and preimplantation embryo development (Kuscu and Celik-Ozenci, 2015). Drosophila STAT (STAT92E) is present in the early embryo as a maternal product, and the expression of this gene is activated during the maternal to zygotic (MZT) process, which plays an important role in transcription of the zygotic genome at the onset of embryonic development (Tsurumi et al, 2011). As a critical transcription factor in early mammalian development, STAT3 has likely been involved in the determination of the animal pole of the oocyte and in the establishment of the inner cell mass and trophoblast in the preimplantation embryos (Zhang et al, 2007). More and more TFs such as ATF3, EN1, IFI16, IKZF3, KLF3, NPAS3, NR2F2, RUNX1, SOX2, ZBTB20, and ZSCAN4 (Godini and Fallahi, 2019) genes were discovered using the new technology of single-cell sequencing

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