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. 2023 Feb 1;41(1):37-42.
doi: 10.7518/hxkq.2023.01.005.

Transcriptome heterogeneity of congenital cleft palate model in congener New Zealand rabbits induced by dexamethasone

[Article in English, Chinese]
Lanling Lin  1 , Haoyue Liu  1 , Xiao Luo  1 , Chong Zhang  1 , Bingshuai Jing  1 , Bing Shi  1 , Chenghao Li  1
Affiliations

Transcriptome heterogeneity of congenital cleft palate model in congener New Zealand rabbits induced by dexamethasone

[Article in English, Chinese]
Lanling Lin et al. Hua Xi Kou Qiang Yi Xue Za Zhi. .

Abstract
in English, Chinese

Objectives: This work aimed to investigate the transcriptome heterogeneity of dexamethasone-induced congenital cleft palate in homozygous New Zealand rabbits and determine the molecular mechanism underlying the occurrence of congenital cleft palate.

Methods: Dexamethasone (1.0 mg per day) was administered intramuscularly to 20 New Zealand pregnant rabbits from day 14 to day 17 of gestation, and the palatal phenotype of all offspring of each pregnant rabbit was observed. Eight embryos with a 4∶4 ratio of cleft palate to non-cleft palate were selected and divided into the cleft palate group (CP) and non-cleft palate group (NCP). Their palatal tissues were collected for RNA sequencing.

Results: A total of 225 differentially expressed genes (Q<0.05) were found in the CP group compared with the NCP group, of which 120 genes were upregulated and 105 genes were downregulated. The GO and KEGG enrichment analyses of these differentially expressed genes were carried out. The results showed significant enrichment in GO classification, which included heterotrimeric G protein complex, extracellular matrix, transcription factor complex, and basement membrane. Meanwhile, GABA ergic synapse, morphine addiction, retrograde endocannabinoid signaling, glutamate synapse, serotonergic synapse, regulation of actin cytoskeleton, and the Apelin signaling pathway were significantly enriched in the KEGG pathway. Compared with the NCP group, the gene expression levels of ARHGEF6 (P<0.05) and ABI2 (P<0.001) decreased in the CP group, and APC increased (P<0.001); these results were confirmed by real-time polymerase chain reaction.

Conclusions: Abnormal expression levels of the ARHGEF6, APC, and ABI2 genes involved in the regulation of the actin cytoskeleton in the palatal synapse may be associated with the dexamethasone-induced congenital cleft palate in New Zealand rabbits.

目的: 研究地塞米松诱导同系新西兰仔兔先天腭裂的转录组异质性，进一步探究先天性腭裂发生的分子机制。方法: 妊娠第14天到第17天给20只新西兰孕兔肌肉注射地塞米松（每天1.0 mg），观察每只孕兔所有子代腭部表型。选取生产了8只胚胎、腭裂胚胎与非腭裂胚胎为4∶4的孕兔，分为腭裂组（CP）与非腭裂组（NCP），收集其腭部组织进行转录组测序分析。结果: CP组与NCP组相比，共有225个差异基因（Q<0.05），其中120个基因上调，105个基因下调。差异性表达基因的GO和KEGG富集分析表明，异三聚体G蛋白复合物、细胞外基质、转录因子复合物、基底膜的GO分类呈显著富集；GABA能突触、吗啡成瘾、逆行内源性大麻素信号、谷氨酸突触、含血清素的神经突触、肌动蛋白细胞骨架的调节、Apelin信号通路等在KEGG通路中显著富集。实时荧光定量分析法验证表明，与NCP组相比，CP组ARHGEF6（P<0.05）、ABI2（P<0.001）基因表达水平下降，APC基因表达水平上升（P<0.001）。结论: 参与腭突中肌动蛋白细胞骨架调节的基因ARHGEF6、APC、ABI2的表达水平异常可能和地塞米松诱导新西兰兔先天性腭裂的形成相关。.

Keywords: congenital cleft palate; cytoskeleton regulation; dexamethasone; transcriptomic analysis.

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Conflict of interest statement

利益冲突声明：作者声明本文无利益冲突。

Figures

图 1
图 1. NCP组与CP组腭部形态
Fig 1 Palatal morphology of NCP group and CP group 左：NCP；右：CP。P：腭突；*：腭部裂隙。
图 2
图 2. 各样本基因表达量分布
Fig 2 Gene expression distribution in each sample
图 3
图 3. 差异基因火山图
Fig 3 Differential gene volcano map Up：CP组上调基因；no-DEGS：无差异基因；Down：CP组下调基因。
图 4
图 4. GO富集分析（左）和KEGG通路分析（右）
Fig 4 Results of GO enrichment analysis (left) and KEGG pathway analysis (right) Rich Ratio代表差异基因中与该Term相关的基因数与差异基因总数的比值，圆圈大小代表基因的多少；Q越小说明富集程度越明显。
图 5
图 5. CP组与NCP组差异基因real-time PCR分析
Fig 5 real-time PCR analysis of differential genes between CP group and NCP group 左：ARHGEF6；中：AB12；右：APC。*P<0.05；***P<0.001。
See this image and copyright information in PMC

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