Journal of Shanghai Jiao Tong University (Medical Science) >

2023 , Vol. 43 >Issue 11: 1384 - 1395

DOI: https://doi.org/10.3969/j.issn.1674-8115.2023.11.006

Basic research

Quantitative analysis of the developmental potential of cells and tissues based on evolutionary conservation of genes and regulatory regions

  • Zhiming WANG ,
  • Ran TONG ,
  • Chen YANG ,
  • Huiyuan JIAO ,
  • Yihao WANG ,
  • Linying LI ,
  • Yexin WANG ,
  • Feng ZHANG ,
  • Lingjie LI
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  • 1.Department of Histoembryology, Genetics and Developmental Biology; Shanghai Key Laboratory of Reproductive Medicine; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
    2.Department of Ophthalmology, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
    3.Department of Central Laboratory, Shanghai Children′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200062, China
    4.Department of Oral Surgery, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
ZHANG Feng, E-mail: fzhang@shsmu.edu.cn. #Co-Corresponding authors.
LI Lingjie, E-mail: lingjie@shsmu.edu.cn

Received date: 2023-06-09

  Accepted date: 2023-10-25

  Online published: 2023-11-28

Supported by

National Key Research and Development Program of China(2021YFA1100400)

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Abstract

Objective ·To study the relationship between evolution and the developmental process from the perspective of DNA sequence conservation, and explore their inherent principles. Methods ·First, conservation rate (CR) was established by analyzing the conservation of amino acid sequences of coding genes in 100 species to quantify the evolutionary conservation of genes. The relationship between CR and developmental potential was verified by using the feature genes involved in embryonic stem cells pathways. Secondly, cell type-specific genes and their characteristics in conservation were studied by analyzing the RNA sequencing (RNA-seq) data of the three early germ layers (ectoderm, mesoderm and endoderm) and their corresponding mature organs (brain, heart, liver, etc). Then, chromatin immunoprecipitation sequencing (ChIP-seq) data of enhancer histone H3 acetylated at lysine 27 (H3K27ac) from early germ layers and mature organs were collected to search for enhancer sites and identify super enhancers in various cells and tissues by using the ROSE procedure. Functional enrichment and signaling pathway analysis of genes was used to examine the identity correlation between SEs-regulated genes and the corresponding cell characteristics, to clarify whether the SEs identified in this study were consistent with the characteristics reported in previous studies. Finally, PhastCons program was used to calculate the DNA conservation score (CS) of non-coding regulatory regions to study their relationship with developmental potential. Results ·In the coding region of DNA, CR was successfully established to quantify the conservation of genes. The gene expression data of early germ layers and mature organs showed that the genes with higher conservation rate were more relevant to the stemness and early developmental process, and the differences between the tissues from early and late development could be distinguished by using CR. In the non-coding regions of DNA, it was found that the conservation of regulatory regions was also correlated with development. The CS of the SE sequences in the early developmental germ layers was significantly higher than that of the SE sequences in the corresponding mature organs. However, cell-specific typical enhancers (TEs) did not show such a trend. Conclusion ·During the developmental process, CR of genes expressed in the coding region decreases, and CS of super-enhancer DNA in the non-coding region decreases.

Key words： embryonic development; evolution; super enhancer; developmental genetics; conservation of DNA

Cite this article

Zhiming WANG , Ran TONG , Chen YANG , Huiyuan JIAO , Yihao WANG , Linying LI , Yexin WANG , Feng ZHANG , Lingjie LI . Quantitative analysis of the developmental potential of cells and tissues based on evolutionary conservation of genes and regulatory regions[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023 , 43(11) : 1384 -1395 . DOI: 10.3969/j.issn.1674-8115.2023.11.006

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