Early pregnancy serum exosomes miRNAs gene-targets vary based on pancreatic β-cell function in GDM

Genes regulated by the miRNA set differentially expressed in maternal or placental serum exosomes in women who will develop GDM based on early pregnancy HOMA-% β index status.
Differential expression of miRNA profiles among study subgroups using Affymetrix Transcriptome Analysis Console (TAC) Software version 4.0.1 (Affymetrix, Applied Biosystems). The results were preprocessed at RMA+DABG-NONORM-Human-only setting. The t-test, Multiple Testing Corrections, and False Discovery Rate Prediction were used for this purpose. Those genes with an FDR-adjusted p-value less than 0.05 demonstrated at least a 2-fold difference between the control group and the contrast subgroups were considered statistically significant and differentially expressed. Microarray data have been deposited in the Gene Expression Omnibus (GEO) database with accession number GSE243374.
Once the DEmiRNAs were identified for each subgroup, target gene prediction for each DEmiRNA identified was performed using TargetScanHuman 8.0 database (20). TargetScanHuman’s cumulative weighted context score (CWCS) of -0.7 or lower was used as a confidence level filter for miRNA targeting. Each CWCS indicates that a microRNA represses a certain mRNA target by at least 38% as compared to the normal baseline level. Once the target genes were identified, gene expression data analysis was performed using ExpressAnalyst (https://www.expressanalyst.ca). Gene expression statistical and functional global enrichment networks using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were generated for each comparison condition between the control and the contrast subgroups. KEGG 2021 Human Pathway analysis were performed using the Enrichr platform.

Table S1. Genes regulated by the miRNA set differentially expressed in maternal serum exosomes in women who will develop GDM with a high HOMA-% β index
Table S2. Genes regulated by the miRNA set differentially expressed in maternal serum exosomes in women who will develop GDM with a low HOMA-% β index
Table S3. Genes regulated by hsa-miR-6724-5p present in maternal serum exosomes in women who will develop GDM regardless of their HOMA-% β index
Table S4. Genes regulated by the miRNA set differentially expressed in placental serum exosomes in women who will develop GDM with a high HOMA-% β index
Table S5. Genes regulated by the miRNA set differentially expressed in placental serum exosomes in women who will develop GDM with a low HOMA-% β index
Table S6. Genes regulated by hsa-miR-3665 identified in placental serum exosomes in women who will develop GDM regardless of their HOMA-% β index

基于早期妊娠HOMA-%β指数状态，未来可能发展为妊娠期糖尿病（GDM）的妇女，其母体或胎盘血清外泌体中由miRNA调控的差异表达基因。利用Affymetrix转录组分析控制台（TAC）软件版本4.0.1（Affymetrix，Applied Biosystems）对研究亚组的miRNA谱进行差异表达分析。结果在RMA+DABG-NONORM-Human-only设置下进行预处理。采用t检验、多重检验校正和假发现率预测等方法进行此目的。FDR调整后的p值小于0.05的基因，在对照组与对比亚组之间至少表现出2倍差异，被视为具有统计学意义的差异表达。微阵列数据已存入基因表达综合数据库（GEO）中，登录号为GSE243374。一旦为每个亚组确定了差异表达miRNA（DEmiRNA），便使用TargetScanHuman 8.0数据库（20）对每个DEmiRNA进行目标基因预测。TargetScanHuman的累积加权上下文得分（CWCS）-0.7或以下被用作miRNA靶向的置信度过滤标准。每个CWCS表明，与正常基线水平相比，一个miRNA至少抑制了38%的特定mRNA靶标。一旦确定了靶基因，便使用ExpressAnalyst（https://www.expressanalyst.ca）进行基因表达数据分析。对于对照组与对比亚组之间的每个比较条件，使用京都基因与基因组百科全书（KEGG）数据库生成了基因表达统计学和功能全局富集网络。KEGG 2021人类通路分析使用Enrichr平台进行。

表S1. 高HOMA-%β指数的妊娠期糖尿病（GDM）孕妇母体血清外泌体中miRNA调控的差异表达基因

表S2. 低HOMA-%β指数的妊娠期糖尿病（GDM）孕妇母体血清外泌体中miRNA调控的差异表达基因

表S3. 无论HOMA-%β指数如何，母体血清外泌体中含hsa-miR-6724-5p的妊娠期糖尿病（GDM）孕妇miRNA调控的差异表达基因

表S4. 高HOMA-%β指数的妊娠期糖尿病（GDM）孕妇胎盘血清外泌体中miRNA调控的差异表达基因

表S5. 低HOMA-%β指数的妊娠期糖尿病（GDM）孕妇胎盘血清外泌体中miRNA调控的差异表达基因

表S6. 无论HOMA-%β指数如何，胎盘血清外泌体中hsa-miR-3665识别的妊娠期糖尿病（GDM）孕妇miRNA调控的差异表达基因