Expression profiling of human immune cell subsets identifies miRNA-mRNA regulatory relationships correlated with cell type specific expression.
Expression profiling of human immune cell subsets identifies miRNA-mRNA regulatory relationships correlated with cell type specific expression.
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DOI：
10.1371/journal.pone.0029979
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Matthes T
中科院分区：
文献类型：
--
作者：
Allantaz F;Cheng DT;Bergauer T;Ravindran P;Rossier MF;Ebeling M;Badi L;Reis B;Bitter H;D'Asaro M;Chiappe A;Sridhar S;Pacheco GD;Burczynski ME;Hochstrasser D;Vonderscher J;Matthes T
血液由具有不同功能和相应不同基因表达谱的不同细胞群组成。在这项研究中，对九种人类免疫细胞亚群（中性粒细胞、嗜酸性粒细胞、单核细胞、B 细胞、NK 细胞、CD4 T 细胞、CD8 T 细胞、mDC 和 pDC）进行了全局 miRNA 表达谱分析，以鉴定细胞类型特异性 miRNA。对同一样本进行 mRNA 表达谱分析，以确定特定细胞类型的 miRNA 是否下调其靶基因的表达水平。六种细胞类型特异性 miRNA（miR-143；中性粒细胞特异性，miR-125；T 细胞和中性粒细胞特异性，miR-500；单核细胞和 pDC 特异性，miR-150；淋巴细胞特异性，miR-652 和 miR-223；均为骨髓细胞特异性）与其预测靶基因的表达呈负相关。使用独立队列进一步验证了这些结果，其中分离了类似的免疫细胞子集并分析了 miRNA 和 mRNA 的表达情况。两个队列中与靶基因表达负相关的 miRNA 被确定为 miRNA/mRNA 调控对的候选者，并用于构建细胞类型特异性调控网络。 miRNA/mRNA 对在网络中形成两个不同的簇，对应于骨髓（九个 miRNA）和淋巴谱系（两个 miRNA）。几种骨髓特异性 miRNA 靶向常见基因，包括 ABL2、EIF4A2、EPC1 和 INO80D；这些共同靶点富含参与基因表达调节的基因（p<9.0E-7）。因此，这些 miRNA 可能通过抑制参与转录调控的基因的表达，对基因表达产生显着的进一步影响。本研究报告的 miRNA 和 mRNA 表达谱形成了各种人类血细胞的综合转录组数据库，并作为阐明 miRNA 介导的调节在建立免疫细胞身份中的作用的宝贵资源。
Blood consists of different cell populations with distinct functions and correspondingly, distinct gene expression profiles. In this study, global miRNA expression profiling was performed across a panel of nine human immune cell subsets (neutrophils, eosinophils, monocytes, B cells, NK cells, CD4 T cells, CD8 T cells, mDCs and pDCs) to identify cell-type specific miRNAs. mRNA expression profiling was performed on the same samples to determine if miRNAs specific to certain cell types down-regulated expression levels of their target genes. Six cell-type specific miRNAs (miR-143; neutrophil specific, miR-125; T cells and neutrophil specific, miR-500; monocyte and pDC specific, miR-150; lymphoid cell specific, miR-652 and miR-223; both myeloid cell specific) were negatively correlated with expression of their predicted target genes. These results were further validated using an independent cohort where similar immune cell subsets were isolated and profiled for both miRNA and mRNA expression. miRNAs which negatively correlated with target gene expression in both cohorts were identified as candidates for miRNA/mRNA regulatory pairs and were used to construct a cell-type specific regulatory network. miRNA/mRNA pairs formed two distinct clusters in the network corresponding to myeloid (nine miRNAs) and lymphoid lineages (two miRNAs). Several myeloid specific miRNAs targeted common genes including ABL2, EIF4A2, EPC1 and INO80D; these common targets were enriched for genes involved in the regulation of gene expression (p<9.0E-7). Those miRNA might therefore have significant further effect on gene expression by repressing the expression of genes involved in transcriptional regulation. The miRNA and mRNA expression profiles reported in this study form a comprehensive transcriptome database of various human blood cells and serve as a valuable resource for elucidating the role of miRNA mediated regulation in the establishment of immune cell identity.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
32.4
作者：
O'Connell RM;Kahn D;Gibson WS;Round JL;Scholz RL;Chaudhuri AA;Kahn ME;Rao DS;Baltimore D
通讯作者：
Baltimore D
影响因子：
5.4
作者：
Chaussabel D;Pascual V;Banchereau J
通讯作者：
Banchereau J
影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
影响因子：
64.8
作者：
Johnnidis, Jonathan B.;Harris, Marian H.;Camargo, Fernando D.
通讯作者：
Camargo, Fernando D.