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. 2025 Jan 8:12:1515524.
doi: 10.3389/fcell.2024.1515524. eCollection 2024.

Study on gene expression in the liver at various developmental stages of human embryos

Hanqing Chen  1 , Tingting Li  2 , Ming Cai  3 , Zhiqi Huang  3 , Jianjun Gao  4 , Hongping Ding  5 , Minmin Li  6 , Weiyu Guan  7 , Jinpeng Chen  3 , Wenran Wang  5 , Chunhong Li  5 , Jianwu Shi  1
Affiliations

Study on gene expression in the liver at various developmental stages of human embryos

Hanqing Chen et al. Front Cell Dev Biol. .

Abstract

Background: The normal development of the liver during human embryonic stages is critical for the functionality of the adult liver. Despite this, the essential genes, biological processes, and signal pathways that drive liver development in human embryos remain poorly understood.

Methods: In this study, liver samples were collected from human embryos at progressive developmental stages, ranging from 2-month-old to 7-month-old. Highly expressed genes and their associated enrichment processes at various developmental stages of the liver were identified through transcriptomic sequencing.

Results: The findings indicated that genes associated with humoral immune responses and B-cell-mediated immunity were highly expressed during the early developmental stages. Concurrently, numerous genes related to vitamin response, brown adipocyte differentiation, T cell differentiation, hormone secretion, hemostasis, peptide hormone response, steroid metabolism, and hematopoietic regulation exhibited increased expression aligned with liver development. Our results suggest that the liver may possess multiple functions during embryonic stages, beyond serving hematopoietic roles. Moreover, this study elucidated the complex regulatory interactions among genes involved in lymphocyte differentiation, the regulation of hemopoiesis, and liver development. Consequently, the development of human embryonic liver necessitates the synergistic regulation of numerous genes. Notably, alongside conventionally recognized genes, numerous previously uncharacterized genes involved in liver development and function were also identified.

Conclusion: These findings establish a critical foundation for future research on liver development and diseases arising from fetal liver abnormalities.

Keywords: development; gene expression; human embryos; livers; transcriptomic sequencing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The genes with high expression levels and biological processes in the liver of 3-month-old human embryo. (A) The volcano plot showed the differentially expressed gene (DEGs) between the livers of 2-month-old and 3-month-old human embryos. (B) A total of 1,112 upregulated and 957 downregulated genes were identified in the liver of 3-month-old human embryo (3-month-old vs. 2-month-old liver). (C) GO analysis of the highly expressed genes identified in the liver of 3-month-old human embryo. (D) KEGG pathway analysis of the highly expressed genes identified in the liver of 3-month-old human embryo. (E) Heatmaps showed the expression of genes associated with humoral immune response in the livers of 2-month-old and 3-month-old human embryos.
FIGURE 2
FIGURE 2
The genes with high expression levels and biological processes in the liver of 4-month-old human embryo. (A) The volcano plot showed the DEGs between the livers of 3-month-old and 4-month-old human embryos. (B) A total of 406 upregulated genes and 513 downregulated genes were identified in the liver of 4-month-old human embryo (4-month-old vs. 3-month-old liver). (C) GO analysis of the highly expressed genes identified in the liver of 4-month-old human embryo. (D) KEGG pathway analysis of the highly expressed genes identified in the liver of 4-month-old human embryo. (E) Heatmaps showed the expression of genes associated with response to vitamin and brown fat cell differentiation in the livers of 3-month-old and 4-month-old human embryos.
FIGURE 3
FIGURE 3
The genes with high expression levels and biological processes in the liver of 5-month-old human embryo. (A) The volcano plot showed the DEGs between the livers of 4-month-old and 5-month-old human embryos. (B) A total of 1,558 upregulated genes and 389 downregulated genes were identified in the liver of 5-month-old human embryo (5-month-old vs. 4-month-old liver). (C) GO analysis of the highly expressed genes identified in the liver of 5-month-old human embryo. (D) KEGG pathway analysis of the highly expressed genes identified in the liver of 5-month-old human embryo. (E) Heatmaps showed the expression of genes associated with T cell differentiation in the livers of 5-month-old and 6-month-old human embryos.
FIGURE 4
FIGURE 4
The genes with high expression levels and biological processes in the liver of 6-month-old human embryo. (A) The volcano plot showed the DEGs between the livers of 5-month-old and 6-month-old human embryos. (B) A total of 643 upregulated genes and 1,607 downregulated genes were identified in the liver of 6-month-old human embryo (6-month-old vs. 5-month-old liver). (C) GO analysis of the highly expressed genes identified in the liver of 6-month-old human embryo. (D) KEGG pathway analysis of the highly expressed genes identified in the liver of 6-month-old human embryo. (E) Heatmaps showed the expression of genes associated with coagulation and hormone transport in the livers of 5-month-old and 6-month-old human embryos.
FIGURE 5
FIGURE 5
The genes with high expression and biological processes in the liver of 7-month-old human embryo. (A) The volcano plot showed the DEGs between the livers of 6-month-old and 7-month-old human embryos. (B) A total of 1,025 upregulated and 1,406 downregulated genes were identified in the liver of 7-month-old human embryo (7-month-old vs. 6-month-old liver). (C) GO analysis of the highly expressed genes identified in the 7-month-old human embryonic liver. (D) KEGG pathway analysis of the highly expressed genes identified in the 7-month-old embryonic liver. (E) Heatmaps showed the expression of genes associated with positive regulation of T cell activation and steroid metabolic process in the livers of 6-month-old and 7-month-old human embryos.
FIGURE 6
FIGURE 6
The expression analysis of genes and associated biological processes along the pseudotime from the 3-month-old to 7-month-old liver. (A) The biological processes of complement activation and blood coagulation along the pseudotime from the 3-month-old to 4-month-old liver, cellular carbohydrate metabolic process and serine family amino acid metabolic process along the pseudotime from the 4-month-old to 5-month-old liver, myeloid leukocyte activation, humoral immune response, T cell proliferation and T cell differentiation along the pseudotime from the 5-month-old to 6-month-old liver, response to peptide hormone, cellular response to peptide hormone stimulus, steroid metabolic process and response to steroid hormone along the pseudotime of the 7-month-old liver, respectively. (B) The expression of SERPING1, HRG, F9, CD36, PPP1R3G, PPP1R3C, PFKFB3, IGFBP3, PIK3CD, MYB, JAK3, FOXO3, APOL2, APOL1, AKR1C1, ADM along the pseudotime from the 3-month-old to 7-month-old liver.
FIGURE 7
FIGURE 7
Validation of the genes associated with the biological processes of the regulation of hemopoiesis, liver development and lymphocyte differentiation. (A) Potential gene interaction networks involved in the regulation of hemopoiesis, liver development and lymphocyte differentiation. (B) Heatmaps illustrate the expression profiles of genes related to the regulation of hemopoiesis, liver development and lymphocyte differentiation between the livers of 6-month-old and 7-month-old human embryos. (C) The expression of genes involved in the regulation of hemopoiesis in the livers of 6-month-old and 7-month-old human embryos using qPCR. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001.
FIGURE 8
FIGURE 8
The expression analysis of genes involved in the regulation of hemopoiesis and liver development. (A) The expression of genes associated with the regulation of hemopoiesis in the livers of 6-month-old and 7-month-old human embryos using qPCR. (B) The expression of genes associated with liver development in the livers of 6-month-old and 7-month-old human embryo using qPCR. (C) The expression level of PCK1 were quantified through Western blot analysis and the statistical analysis of protein level of PCK1. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001.
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