Functional and gene network analyses of transcriptional signatures characterizing pre-weaned bovine mammary parenchyma or fat pad uncovered novel inter-tissue signaling networks during development.
Functional and gene network analyses of transcriptional signatures characterizing pre-weaned bovine mammary parenchyma or fat pad uncovered novel inter-tissue signaling networks during development.
复制标题
DOI：
10.1186/1471-2164-11-331
复制
发表时间：
2010-05-26
期刊：
影响因子：
4.4
通讯作者：
Loor JJ
中科院分区：
文献类型：
--
作者：
Piantoni P;Bionaz M;Graugnard DE;Daniels KM;Everts RE;Rodriguez-Zas SL;Lewin HA;Hurley HL;Akers M;Loor JJ
新生牛乳腺脂肪垫（MFP）周围的乳腺实质（PAR）被认为是通过分泌局部生长调节剂的全身激素诱导的PAR的增殖作用。我们使用生物信息学来表征PAR和MFP之间的转录组学差异从~65日龄荷斯坦小母牛。通过分析一种组织相对于另一种组织优先表达的信号分子，挖掘数据以揭示潜在的串扰。发现了超过9，000个差异表达基因（DEG;错误发现率≤ 0.05），其中1，478个在PAR和MFP之间差异≥1.5倍。在PAR与MFP（n = 736）中高表达的DEG中，我们注意到与细胞周期、结构组织、信号传导和DNA/RNA代谢相关的功能显著富集。只有肌动蛋白细胞骨架信号是显着的经典途径。DEG在MFP中比PAR（n = 742）更高表达，属于脂质代谢、信号传导、细胞运动和免疫相关功能。与代谢和信号传导相关的典型途径，特别是免疫和代谢相关的途径显著丰富。网络分析揭示了MYC、TP 53和CTNNB 1在控制DEG表达中的核心作用，DEG在PAR与MFP中高度表达。类似的分析表明，PPARG、KLF 2、EGR 2和EPAS 1在调节MFP与PAR中更高表达的DEG的表达中起核心作用。基因网络分析揭示了优先在一个组织中表达的细胞因子和生长因子之间的推定的组织间串扰（例如，PAR与MFP中的ANGPTL 1、SPP 1、IL 1B; MFP与PAR中的ADIPOQ、IL 13、FGF 2、LEP），DEG优先在其他组织中表达，特别是转录因子或途径（例如，PAR与MFP中的MYC、TP 53和肌动蛋白细胞骨架信号传导; MFP与PAR中的PPARG和LXR/RXR信号传导）。功能分析强调了确定MFP和PAR的生物学特征在新生儿发育过程中的相互影响。这通过信号分子（细胞因子、生长因子）优先释放（即，更高表达的）可能具有在MFP或PAR中富集的分子功能或信号通路。这些双向相互作用可能需要在正常情况下或响应营养来协调乳腺组织发育。
The neonatal bovine mammary fat pad (MFP) surrounding the mammary parenchyma (PAR) is thought to exert proliferative effects on the PAR through secretion of local modulators of growth induced by systemic hormones. We used bioinformatics to characterize transcriptomics differences between PAR and MFP from ~65 d old Holstein heifers. Data were mined to uncover potential crosstalk through the analyses of signaling molecules preferentially expressed in one tissue relative to the other. Over 9,000 differentially expressed genes (DEG; False discovery rate ≤ 0.05) were found of which 1,478 had a ≥1.5-fold difference between PAR and MFP. Within the DEG highly-expressed in PAR vs. MFP (n = 736) we noted significant enrichment of functions related to cell cycle, structural organization, signaling, and DNA/RNA metabolism. Only actin cytoskeletal signaling was significant among canonical pathways. DEG more highly-expressed in MFP vs. PAR (n = 742) belong to lipid metabolism, signaling, cell movement, and immune-related functions. Canonical pathways associated with metabolism and signaling, particularly immune- and metabolism-related were significantly-enriched. Network analysis uncovered a central role of MYC, TP53, and CTNNB1 in controlling expression of DEG highly-expressed in PAR vs. MFP. Similar analysis suggested a central role for PPARG, KLF2, EGR2, and EPAS1 in regulating expression of more highly-expressed DEG in MFP vs. PAR. Gene network analyses revealed putative inter-tissue crosstalk between cytokines and growth factors preferentially expressed in one tissue (e.g., ANGPTL1, SPP1, IL1B in PAR vs. MFP; ADIPOQ, IL13, FGF2, LEP in MFP vs. PAR) with DEG preferentially expressed in the other tissue, particularly transcription factors or pathways (e.g., MYC, TP53, and actin cytoskeletal signaling in PAR vs. MFP; PPARG and LXR/RXR Signaling in MFP vs. PAR). Functional analyses underscored a reciprocal influence in determining the biological features of MFP and PAR during neonatal development. This was exemplified by the potential effect that the signaling molecules (cytokines, growth factors) released preferentially (i.e., more highly-expressed) by PAR or MFP could have on molecular functions or signaling pathways enriched in the MFP or PAR. These bidirectional interactions might be required to coordinate mammary tissue development under normal circumstances or in response to nutrition.
登录
查看更多内容
影响因子：
3.5
作者：
Connor, E. E.;Meyer, M. J.;Capuco, A. V.
通讯作者：
Capuco, A. V.
影响因子：
3.5
作者：
Akers, RM
通讯作者：
Akers, RM
DOI：
10.1038/nrm2467
发表时间：
2008-10
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.2
作者：
Capuco, Anthony V.
通讯作者：
Capuco, Anthony V.
影响因子：
3.5
作者：
Daniels, K. M.;Hill, S. R.;Akers, R. M.
通讯作者：
Akers, R. M.