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. 2025 May 30:13:1564789.
doi: 10.3389/fcell.2025.1564789. eCollection 2025.

Study on gene expression in stomach at different developmental stages of human embryos

Weiyu Guan  1 , Xinran Lu  1 , Yin Zhang  2 , Hongping Ding  2 , Xinmei Liu  3 , Le Yang  3 , Wenran Wang  2 , Jianwu Shi  3 , Shichun Feng  1
Affiliations

Study on gene expression in stomach at different developmental stages of human embryos

Weiyu Guan et al. Front Cell Dev Biol. .

Abstract

Background: The proper development of embryonic stomach in human is essential for the functionality of the adult stomach. However, the key genes, biological processes, and signaling pathways that influence stomach development in human embryogenesis are not yet fully understood.

Methods: In this study, stomach samples were obtained from human embryos at developmental stages ranging from two to seven months. Through transcriptomic sequencing, we identified the differentially expressed genes and enrichment processes in the stomach at various developmental phases.

Results: The results of this study indicate that genes associated with embryonic organ morphogenesis, digestive tract development, and gastric acid secretion displayed elevated expression during the early developmental stages. Additionally, a number of genes linked to cilium assembly and organization, peptide and hormone secretion and transportation, and immune response, showed increased expression during stomach maturation. Our findings elucidate that both the morphological and functional aspects of the stomach develop during the early stages of embryonic development. As gastric development, the stomach progressively acquires additional functions. This research provides insights into the intricate regulatory networks among the genes involved in embryonic digestive tract development, digestion and embryonic organ morphogenesis. Therefore, the formation of human embryonic stomach necessitates the synergistic regulation of a plethora of genes. Notably, this study not only identified traditionally recognized genes but also revealed many previously uncharacterized genes that play potential roles in stomach development and its functions.

Conclusion: These findings establish a crucial basis for future studies on stomach development and the disorders arising from fetal stomach abnormalities.

Keywords: development; gene expression; human embryos; stomachs; 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
Analysis of the highly expressed genes and biological processes in the stomach of 3-month-old human embryo. (A) Volcano plot illustrating the differentially expressed genes (DEGs) between the 2-month-old and 3-month-old stomachs. (B) Statistical analysis of 4,222 upregulated and 2,374 downregulated genes in the stomach of 3-month-old embryo. (C) Gene Ontology (GO) analysis of the upregulated genes identified in the stomach of 3-month-old embryo. (D) KEGG pathway analysis of the upregulated genes identified in the stomach of 3-month-old embryo. (E) Heatmap revealed the expression genes related to digestive system development in the 2-month-old and 3-month-old stomachs. (F) Heatmap revealed the expression genes related to axon guidance in the 2-month-old and 3-month-old stomachs.
FIGURE 2
FIGURE 2
Analysis of the highly expressed genes and biological processes in the stomach of 4-month-old human embryo. (A) Volcano plot illustrating the differentially expressed genes (DEGs) between the 3-month-old and 4-month-old stomachs. (B) Statistical analysis of 2,363 upregulated and 1,224 downregulated genes in the stomach of 4-month-old embryo. (C) GO analysis of the upregulated genes in the stomach tissue of 4-month-old embryo. (D) KEGG pathway analysis of the upregulated genes identified in the stomach of 4-month-old embryo. (E) Heatmap revealed the expression genes related to cilium organization in the stomachs of 3-month-old and 4-month-old embryos.
FIGURE 3
FIGURE 3
Analysis of the highly expressed genes and biological processes in the stomach of 5-month-old human embryo. (A) Volcano plot illustrating the differentially expressed genes (DEGs) between the stomach tissues of 4-month-old and 5-month-old embryos. (B) Statistical analysis of 688 upregulated and 2,666 downregulated genes in the stomach of 5-month-old embryo. (C) GO analysis of the upregulated genes in the stomach tissue of 5-month-old embryo. (D) KEGG pathway analysis of the upregulated genes identified in the stomach of 5-month-old embryo. (E) Heatmap revealed the expression genes related to gastric acid secretion in the 4-month-old and 5-month-old stomachs.
FIGURE 4
FIGURE 4
Analysis of the highly expressed genes and biological processes in the stomach of 6-month-old human embryo. (A) Volcano plot illustrating the differentially expressed genes (DEGs) between the stomach tissues of 5-month-old and 6-month-old embryos. (B) Statistical analysis of 1,498 upregulated and 1,187 downregulated genes in the stomach of 6-month-old embryo. (C) GO analysis of the upregulated genes in the stomach tissue of 6-month-old embryo. (D) KEGG pathway analysis of the upregulated genes identified in the stomach of 6-month-old embryo. (E) Heatmap revealed the expression genes related to hormone secretion in the stomachs of 5-month-old and 6-month-old embryos.
FIGURE 5
FIGURE 5
Analysis of the highly expressed genes and biological processes in the stomach of 7-month-old human embryo. (A) Volcano plot illustrating the differentially expressed genes (DEGs) between the stomach tissues of 6-month-old and 7-month-old embryos. (B) Statistical analysis of 1,141 upregulated and 2,037 downregulated in the stomach of 7-month-old embryo. (C) GO analysis of the upregulated genes in the stomach tissue of 7-month-old embryo. (D) KEGG pathway analysis of the upregulated genes identified in the stomach of 7-month-old embryo. (E) Heatmap revealed the expression genes related to T cell activation in the stomachs of 6-month-old and 7-month-old embryos.
FIGURE 6
FIGURE 6
Analysis of the genes and biological processes along the pseudotime from the 3-month-old to 7-month-old stomach. (A) The biological processes of collagen metabolic process and hemostasis, cilium movement and regionalization, response to steroid hormone and digestion, regulation of vasculature development and regulation of leukocyte proliferation along the pseudotime from the 3-month-old to 7-month-old stomach. (B) The expression of MMP14, MRC2, PCOLCE, VIM, MMP2, COL5A1, DDR2, EMILIN1, MFAP4 along the pseudotime from the 3-month-old to 7-month-old embryonic stomach.
FIGURE 7
FIGURE 7
The regulatory network associated with stomach development. (A) The interaction networks associated with 10 biological processes of the upregulated genes in the stomach of 3-month-old embryo. (B) The interaction networks of genes associated with embryonic digestive tract development, digestion and embryonic organ morphogenesis. (C) The heatmap showed the expression of genes associated with embryonic digestive tract development, digestion and embryonic organ morphogenesis between the 2-month-old and 3-month-old stomachs.
FIGURE 8
FIGURE 8
Verification of genes associated with embryonic digestive tract development and digestion. (A) The expression of genes associated with embryonic digestive tract development in the stomachs of 2-month-old and 3-month-old human embryos using qPCR. (B) The expression of genes involved in digestion in the stomachs of 2-month-old and 3-month-old human embryos using qPCR (*P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001).
FIGURE 9
FIGURE 9
Verification of genes associated with digestion and embryonic organ morphogenesis. (A) The expression of genes associated with digestion in the stomachs of 2-month-old and 3-month-old human embryos using qPCR. (B) The expression of genes involved in embryonic organ morphogenesis in the stomachs of 2-month-old and 3-month-old human embryos using qPCR (*P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001).
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