A module of human peripheral blood mononuclear cell transcriptional network containing primitive and differentiation markers is related to specific cardiovascular health variables.
A module of human peripheral blood mononuclear cell transcriptional network containing primitive and differentiation markers is related to specific cardiovascular health variables.
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DOI：
10.1371/journal.pone.0095124
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Moldovan NI
中科院分区：
文献类型：
--
作者：
Moldovan L;Anghelina M;Kantor T;Jones D;Ramadan E;Xiang Y;Huang K;Kolipaka A;Malarkey W;Ghasemzadeh N;Mohler PJ;Quyyumi A;Moldovan NI
外周血单个核细胞(PBMC)，包括罕见的循环干细胞和祖细胞(CSPC)，在血管和灌流器官的维持和修复中具有重要但知之甚少的作用。我们的假设是，CSPC在心血管健康中的身份和功能可以通过分析它们在未选定的PBMC样本中共表达的标志物的模式来确定。由于基因芯片未能检测到许多干细胞相关基因，我们采用实时定量聚合酶链式反应检测了45个原始和组织分化标志物在健康人和高血压患者PBMC中的表达。我们将这些表达水平与受试者的人口统计和心血管风险因素进行了比较，包括血管僵硬。测试的标记基因在所有样本中都有表达，并以层次化的转录网络模块进行组织，采用自下而上的方法构建。其中一个模块的基因表达指数(Metagene)，定义为15个多能性和心血管分化标志物的平均标准化相对拷贝数，与年龄(R2 = −0.23)、血管硬度(R2 = −0.24)和中心动脉压(R2 = −0.19)呈负相关(P均为0.03)，与体重指数(R2 = 0.72)呈正相关。用mRNA原位杂交和免疫细胞化学方法在单细胞水平上验证了3种新生血管标志物的共同表达。与对照组相比，患者心血管模块基因总表达水平降低了72±22%。然而，在患者的样本中，这两个模块的紧凑度都增加了，这反映在他们的节点连接度的分散程度减少，这表明患者的CSPC具有更原始的特征。综上所述，我们的结果表明CSPC和血管功能之间的关系编码在PBMCs转录网络的模块中。此外，这些模块中的协调基因表达可能与心血管危险因素和亚临床心血管疾病有关；因此，这一指标可能有助于它们的诊断和预后。
Peripheral blood mononuclear cells (PBMCs), including rare circulating stem and progenitor cells (CSPCs), have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their co-expressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects' demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules, constructed by a bottom-up approach. An index of gene expression in one of these modules (metagene), defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p<0.03) with age (R2 = −0.23), vascular stiffness (R2 = −0.24), and central aortic pressure (R2 = −0.19) and positively correlated with body mass index (R2 = 0.72, in women). The co-expression of three neovascular markers was validated at the single-cell level using mRNA in situ hybridization and immunocytochemistry. The overall gene expression in this cardiovascular module was reduced by 72±22% in the patients compared with controls. However, the compactness of both modules was increased in the patients' samples, which was reflected in reduced dispersion of their nodes' degrees of connectivity, suggesting a more primitive character of the patients' CSPCs. In conclusion, our results show that the relationship between CSPCs and vascular function is encoded in modules of the PBMCs transcriptional network. Furthermore, the coordinated gene expression in these modules can be linked to cardiovascular risk factors and subclinical cardiovascular disease; thus, this measure may be useful for their diagnosis and prognosis.
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影响因子：
4.4
作者：
Damughatla, Anirudh R.;Raterman, Brian;Sharkey-Toppen, Travis;Jin, Ning;Simonetti, Orlando P.;White, Richard D.;Kolipaka, Arunark
通讯作者：
Kolipaka, Arunark
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
DOI：
10.1073/pnas.0504271103
发表时间：
2006-01-03
影响因子：
11.1
作者：
Gavrilin, MA;Bouakl, IJ;Wewers, MD
通讯作者：
Wewers, MD
影响因子：
2.1
作者：
Dong, Chunming;Goldschmidt-Clermont, Pascal J
通讯作者：
Goldschmidt-Clermont, Pascal J