Single-cell dissection of transcriptional heterogeneity in human colon tumors.
Single-cell dissection of transcriptional heterogeneity in human colon tumors.
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DOI：
10.1038/nbt.2038
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发表时间：
2011-11-13
影响因子：
46.9
通讯作者：
中科院分区：
文献类型：
--
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癌症通常被认为是正常发育过程的讽刺画，但其细胞异质性真正重演正常组织的多谱系分化过程的程度仍然未知。在这里，我们实施“单细胞PCR基因表达分析”（SINCE-PCR），以解剖原代人正常结肠和结肠癌上皮细胞的组成。我们发现，人类结肠癌组织中含有不同的细胞群体，其转录身份反映了正常结肠的不同细胞谱系。通过从注射单细胞（n = 1）创建单克隆肿瘤异种移植物，我们表明癌组织的转录多样性在很大程度上由体内多谱系分化来解释，而不仅仅是由克隆遗传异质性来解释。最后，我们表明，干扰基因表达程序与多谱系分化密切相关的患者生存。在SINCE-PCR数据的指导下，我们开发了双基因分类系统（KRT 20 vs CA 1，MS 4A 12，CD 177，SLC 26 A3），其预测临床结果的风险比上级于病理级别，并与微阵列衍生的多基因表达特征相当。
Cancer is often viewed as a caricature of normal developmental processes, but the extent by which its cellular heterogeneity truly recapitulates multi-lineage differentiation processes of normal tissues remains unknown. Here, we implement “single-cell PCR gene-expression analysis” (SINCE-PCR) to dissect the cellular composition of primary human normal colon and colon cancer epithelia. We show that human colon cancer tissues contain distinct cell populations whose transcriptional identities mirror those of the different cellular lineages of normal colon. By creating monoclonal tumor xenografts from injection of a single-cell (n = 1), we show that transcriptional diversity of cancer tissues is largely explained by in vivo multi-lineage differentiation, not only by clonal genetic heterogeneity. Finally, we show that perturbations in gene-expression programs linked to multi-lineage differentiation strongly associate with patient survival. Guided by SINCE-PCR data, we develop two-gene classifier systems (KRT20 vs CA1, MS4A12, CD177, SLC26A3) that predict clinical outcomes with hazard-ratios superior to pathological grade and comparable to microarray-derived multi-gene expression signatures.
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影响因子：
11.2
作者：
Odoux, Christine;Fohrer, Helene;Hoppo, Toshitaka;Guzik, Lynda;Stolz, Donna Beer;Lewis, Dale W.;Gollin, Susanne M.;Gamblin, T. Clark;Geller, David A.;Lagasse, Eric
通讯作者：
Lagasse, Eric
影响因子：
4.7
作者：
Losi, L;Baisse, B;Benhattar, J
通讯作者：
Benhattar, J
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
11.8
作者：
Guo, Guoji;Huss, Mikael;Robson, Paul
通讯作者：
Robson, Paul
影响因子：
7.5
作者：
Lugli, Alessandro;Tzankov, Alexandar;Terracciano, Luigi Maria
通讯作者：
Terracciano, Luigi Maria