Human stem cell cultures from cleft lip/palate patients show enrichment of transcripts involved in extracellular matrix modeling by comparison to controls.
Human stem cell cultures from cleft lip/palate patients show enrichment of transcripts involved in extracellular matrix modeling by comparison to controls.
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DOI：
10.1007/s12015-010-9197-3
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发表时间：
2011-06
影响因子：
4.8
通讯作者：
Passos-Bueno, Maria Rita
中科院分区：
文献类型：
--
作者：
Bueno, Daniela Franco;Sunaga, Daniele Yumi;Kobayashi, Gerson Shigeru;Aguena, Meire;Raposo-Amaral, Cassio Eduardo;Masotti, Cibele;Cruz, Lucas Alvizi;Pearson, Peter Lees;Passos-Bueno, Maria Rita
关键词：
非综合征性唇腭裂(NSCL/P)是一种因面原基融合失败而导致的复杂疾病，是一个复杂的发育过程，包括上皮-间充质转化(EMT)。检测NSCL/P患者和对照组之间的差异基因转录为研究与疾病表现有关的途径提供了一个有趣的选择。本研究比较了6例NSCL/P患者和6例正常对照牙髓干细胞(DPSC)的转录组。共鉴定出87个差异表达基因(Deg)。最重要的基因网络由87个核苷酸中的13个组成，其中8个编码胞外蛋白：Acan、COL4A1、COL4A2、GDF15、IGF2、MMP1、MMP3和PDGFa。通过聚类分析，我们还观察到MMP3、Acan、COL4A1和COL4A2表现出共同调节的表达。有趣的是，已知MMP3可裂解多种细胞外蛋白，包括IV、V、IX、X胶原蛋白、蛋白多糖、纤维连接蛋白和层粘连蛋白。它还能够激活其他MMP。此外，以前发现MMP3与NSCL/P有关，在进一步的样本中观察到相同的一般模式，证实参与了NSCL/P患者和对照组之间不同的同步基因表达模式。这些结果显示了我们使用RankProd方法检测差异表达基因的方法的稳健性。总之，NSCL/P患者的DPSCs表现出与细胞外基质建模和腭部EMT过程相关的基因表达特征，这与对照组观察到的不同。这种比较方法应该比传统的基因作图技术更快地识别出易患这种复杂畸形综合征的基因网络。本文的在线版本(doi：10.1007/s12015.0109197-3)包含补充材料，可供授权用户使用。
Nonsyndromic cleft lip and palate (NSCL/P) is a complex disease resulting from failure of fusion of facial primordia, a complex developmental process that includes the epithelial-mesenchymal transition (EMT). Detection of differential gene transcription between NSCL/P patients and control individuals offers an interesting alternative for investigating pathways involved in disease manifestation. Here we compared the transcriptome of 6 dental pulp stem cell (DPSC) cultures from NSCL/P patients and 6 controls. Eighty-seven differentially expressed genes (DEGs) were identified. The most significant putative gene network comprised 13 out of 87 DEGs of which 8 encode extracellular proteins: ACAN, COL4A1, COL4A2, GDF15, IGF2, MMP1, MMP3 and PDGFa. Through clustering analyses we also observed that MMP3, ACAN, COL4A1 and COL4A2 exhibit co-regulated expression. Interestingly, it is known that MMP3 cleavages a wide range of extracellular proteins, including the collagens IV, V, IX, X, proteoglycans, fibronectin and laminin. It is also capable of activating other MMPs. Moreover, MMP3 had previously been associated with NSCL/P. The same general pattern was observed in a further sample, confirming involvement of synchronized gene expression patterns which differed between NSCL/P patients and controls. These results show the robustness of our methodology for the detection of differentially expressed genes using the RankProd method. In conclusion, DPSCs from NSCL/P patients exhibit gene expression signatures involving genes associated with mechanisms of extracellular matrix modeling and palate EMT processes which differ from those observed in controls. This comparative approach should lead to a more rapid identification of gene networks predisposing to this complex malformation syndrome than conventional gene mapping technologies. The online version of this article (doi:10.1007/s12015-010-9197-3) contains supplementary material, which is available to authorized users.
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影响因子：
5.8
作者：
Eichler, GS;Huang, S;Ingber, DE
通讯作者：
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影响因子：
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作者：
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影响因子：
4.1
作者：
Gunaseeli I;Doss MX;Antzelevitch C;Hescheler J;Sachinidis A
通讯作者：
Sachinidis A
影响因子：
3.7
作者：
Grenier, Julien;Teillet, Marie-Aimee;Grifone, Raphaelle;Kelly, Robert G.;Duprez, Delphine
通讯作者：
Duprez, Delphine