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Cited by 703

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Single-cell dissection of transcriptional heterogeneity in human colon tumors

Open access
Dalerba, Piero, Kalisky, Tomer, Sahoo, Debashis, Rajendran, Pradeep S, Rothenberg, Michael E, Leyrat, Anne A, Sim, Sopheak, Okamoto, Jennifer, Johnston, Darius M, Qian, Dalong, Zabala, Maider, Bueno, Janet, Neff, Norma F, Wang, Jianbin, Shelton, Andrew A, Visser, Brendan, Hisamori, Shigeo, Shimono, Yohei, van de Wetering, Marc, Clevers, Hans, Clarke, Michael F, Quake, Stephen R·2011·Nature Biotechnology

Abstract

Cancer is often viewed as a caricature of normal developmental processes, but the extent to which its cellular heterogeneity truly recapitulates multilineage differentiation processes of normal tissues remains unknown. Here we implement single-cell PCR gene-expression analysis 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 (n = 1) cell, we demonstrate that the transcriptional diversity of cancer tissues is largely explained by in vivo multilineage differentiation and not only by clonal genetic heterogeneity. Finally, we show that the different gene-expression programs linked to multilineage differentiation are strongly associated with patient survival. We develop two-gene classifier systems (KRT20 versus CA1, MS4A12, CD177, SLC26A3) that predict clinical outcomes with hazard ratios superior to those of pathological grade and comparable to those of microarray-derived multigene expression signatures.

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Metadata

Authors
Dalerba, P., Kalisky, T., Sahoo, D., Rajendran, P. S., Rothenberg, M. E., Leyrat, A. A., Sim, S., Okamoto, J., Johnston, D. M., Qian, D., Zabala, M., Bueno, J., Neff, N. F., Wang, J., Shelton, A. A., Visser, B., Hisamori, S., Shimono, Y., van de Wetering, M., Clevers, H., Clarke, M. F., & Quake, S. R.
Venue
Nature Biotechnology
Published
2011-11-13
Volume
29
Issue
12
Pages
1120-1127
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W1984984201
Cited by
703
References
5
FWCI
21.87
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Single-cell dissection of transcriptional heterogeneity in human colon tumors. https://app.cochat.ai/papers/10.1038/nbt.2038
The paper
Dalerba, P., Kalisky, T., Sahoo, D., Rajendran, P. S., Rothenberg, M. E., Leyrat, A. A., Sim, S., Okamoto, J., Johnston, D. M., Qian, D., Zabala, M., Bueno, J., Neff, N. F., Wang, J., Shelton, A. A., Visser, B., Hisamori, S., Shimono, Y., van de Wetering, M., . . . Quake, S. R. (2011). Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nature Biotechnology. https://doi.org/10.1038/nbt.2038

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.