Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer

Eunae You; Patrick Danaher; Chenyue Lu; Siyu Sun; Luli Zou; Ildiko E. Phillips; Alexandra S. Rojas; Natalie I. Ho; Yuhui Song; Michael J. Raabe; Katherine H. Xu; Peter M. Richieri; Hao Li; Natalie Aston; Rebecca L. Porter; Bidish K. Patel; Linda T. Nieman; Nathan Schurman; Briana M. Hudson; Khrystyna North; Sarah E. Church; Vikram Deshpande; Andrew S. Liss; Tae K. Kim; Yi Cui; Youngmi Kim; Benjamin D. Greenbaum; Martin J. Aryee; David T. Ting

doi:10.1016/j.cell.2024.09.024

Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer

Eunae You, Patrick Danaher, Chenyue Lu, Siyu Sun, Luli Zou, Ildiko E. Phillips, Alexandra S. Rojas, Natalie I. Ho, Yuhui Song, Michael J. Raabe, Katherine H. Xu, Peter M. Richieri, Hao Li, Natalie Aston, Rebecca L. Porter, Bidish K. Patel, Linda T. Nieman, Nathan Schurman, Briana M. Hudson, Khrystyna NorthSarah E. Church, Vikram Deshpande, Andrew S. Liss, Tae K. Kim, Yi Cui, Youngmi Kim, Benjamin D. Greenbaum, Martin J. Aryee, David T. Ting

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Aberrant expression of repeat RNAs in pancreatic ductal adenocarcinoma (PDAC) mimics viral-like responses with implications on tumor cell state and the response of the surrounding microenvironment. To better understand the relationship of repeat RNAs in human PDAC, we performed spatial molecular imaging at single-cell resolution in 46 primary tumors, revealing correlations of high repeat RNA expression with alterations in epithelial state in PDAC cells and myofibroblast phenotype in cancer-associated fibroblasts (CAFs). This loss of cellular identity is observed with dosing of extracellular vesicles (EVs) and individual repeat RNAs of PDAC and CAF cell culture models pointing to cell-cell intercommunication of these viral-like elements. Differences in PDAC and CAF responses are driven by distinct innate immune signaling through interferon regulatory transcription factor 3 (IRF3). The cell-context-specific viral-like responses to repeat RNAs provide a mechanism for modulation of cellular plasticity in diverse cell types in the PDAC microenvironment.

Original language	English
Pages (from-to)	7232-7247.e23
Journal	Cell
Volume	187
Issue number	25
DOIs	https://doi.org/10.1016/j.cell.2024.09.024
State	Published - 12 Dec 2024
Externally published	Yes

Keywords

cancer-associated fibroblast
cellular plasticity
extracellular vesicles
pancreatic cancer
repeat RNA

Access to Document

10.1016/j.cell.2024.09.024

Cite this

You, E., Danaher, P., Lu, C., Sun, S., Zou, L., Phillips, I. E., Rojas, A. S., Ho, N. I., Song, Y., Raabe, M. J., Xu, K. H., Richieri, P. M., Li, H., Aston, N., Porter, R. L., Patel, B. K., Nieman, L. T., Schurman, N., Hudson, B. M., ... Ting, D. T. (2024). Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer. Cell, 187(25), 7232-7247.e23. https://doi.org/10.1016/j.cell.2024.09.024

@article{dd39ce8cb0084cf3a5129cba554db879,

title = "Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer",

abstract = "Aberrant expression of repeat RNAs in pancreatic ductal adenocarcinoma (PDAC) mimics viral-like responses with implications on tumor cell state and the response of the surrounding microenvironment. To better understand the relationship of repeat RNAs in human PDAC, we performed spatial molecular imaging at single-cell resolution in 46 primary tumors, revealing correlations of high repeat RNA expression with alterations in epithelial state in PDAC cells and myofibroblast phenotype in cancer-associated fibroblasts (CAFs). This loss of cellular identity is observed with dosing of extracellular vesicles (EVs) and individual repeat RNAs of PDAC and CAF cell culture models pointing to cell-cell intercommunication of these viral-like elements. Differences in PDAC and CAF responses are driven by distinct innate immune signaling through interferon regulatory transcription factor 3 (IRF3). The cell-context-specific viral-like responses to repeat RNAs provide a mechanism for modulation of cellular plasticity in diverse cell types in the PDAC microenvironment.",

keywords = "cancer-associated fibroblast, cellular plasticity, extracellular vesicles, pancreatic cancer, repeat RNA",

author = "Eunae You and Patrick Danaher and Chenyue Lu and Siyu Sun and Luli Zou and Phillips, {Ildiko E.} and Rojas, {Alexandra S.} and Ho, {Natalie I.} and Yuhui Song and Raabe, {Michael J.} and Xu, {Katherine H.} and Richieri, {Peter M.} and Hao Li and Natalie Aston and Porter, {Rebecca L.} and Patel, {Bidish K.} and Nieman, {Linda T.} and Nathan Schurman and Hudson, {Briana M.} and Khrystyna North and Church, {Sarah E.} and Vikram Deshpande and Liss, {Andrew S.} and Kim, {Tae K.} and Yi Cui and Youngmi Kim and Greenbaum, {Benjamin D.} and Aryee, {Martin J.} and Ting, {David T.}",

note = "Publisher Copyright: {\textcopyright} 2024 Elsevier Inc.",

year = "2024",

month = dec,

day = "12",

doi = "10.1016/j.cell.2024.09.024",

language = "English",

volume = "187",

pages = "7232--7247.e23",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "25",

}

You, E, Danaher, P, Lu, C, Sun, S, Zou, L, Phillips, IE, Rojas, AS, Ho, NI, Song, Y, Raabe, MJ, Xu, KH, Richieri, PM, Li, H, Aston, N, Porter, RL, Patel, BK, Nieman, LT, Schurman, N, Hudson, BM, North, K, Church, SE, Deshpande, V, Liss, AS, Kim, TK, Cui, Y, Kim, Y, Greenbaum, BD, Aryee, MJ & Ting, DT 2024, 'Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer', Cell, vol. 187, no. 25, pp. 7232-7247.e23. https://doi.org/10.1016/j.cell.2024.09.024

TY - JOUR

T1 - Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer

AU - You, Eunae

AU - Danaher, Patrick

AU - Lu, Chenyue

AU - Sun, Siyu

AU - Zou, Luli

AU - Phillips, Ildiko E.

AU - Rojas, Alexandra S.

AU - Ho, Natalie I.

AU - Song, Yuhui

AU - Raabe, Michael J.

AU - Xu, Katherine H.

AU - Richieri, Peter M.

AU - Li, Hao

AU - Aston, Natalie

AU - Porter, Rebecca L.

AU - Patel, Bidish K.

AU - Nieman, Linda T.

AU - Schurman, Nathan

AU - Hudson, Briana M.

AU - North, Khrystyna

AU - Church, Sarah E.

AU - Deshpande, Vikram

AU - Liss, Andrew S.

AU - Kim, Tae K.

AU - Cui, Yi

AU - Kim, Youngmi

AU - Greenbaum, Benjamin D.

AU - Aryee, Martin J.

AU - Ting, David T.

PY - 2024/12/12

Y1 - 2024/12/12

N2 - Aberrant expression of repeat RNAs in pancreatic ductal adenocarcinoma (PDAC) mimics viral-like responses with implications on tumor cell state and the response of the surrounding microenvironment. To better understand the relationship of repeat RNAs in human PDAC, we performed spatial molecular imaging at single-cell resolution in 46 primary tumors, revealing correlations of high repeat RNA expression with alterations in epithelial state in PDAC cells and myofibroblast phenotype in cancer-associated fibroblasts (CAFs). This loss of cellular identity is observed with dosing of extracellular vesicles (EVs) and individual repeat RNAs of PDAC and CAF cell culture models pointing to cell-cell intercommunication of these viral-like elements. Differences in PDAC and CAF responses are driven by distinct innate immune signaling through interferon regulatory transcription factor 3 (IRF3). The cell-context-specific viral-like responses to repeat RNAs provide a mechanism for modulation of cellular plasticity in diverse cell types in the PDAC microenvironment.

AB - Aberrant expression of repeat RNAs in pancreatic ductal adenocarcinoma (PDAC) mimics viral-like responses with implications on tumor cell state and the response of the surrounding microenvironment. To better understand the relationship of repeat RNAs in human PDAC, we performed spatial molecular imaging at single-cell resolution in 46 primary tumors, revealing correlations of high repeat RNA expression with alterations in epithelial state in PDAC cells and myofibroblast phenotype in cancer-associated fibroblasts (CAFs). This loss of cellular identity is observed with dosing of extracellular vesicles (EVs) and individual repeat RNAs of PDAC and CAF cell culture models pointing to cell-cell intercommunication of these viral-like elements. Differences in PDAC and CAF responses are driven by distinct innate immune signaling through interferon regulatory transcription factor 3 (IRF3). The cell-context-specific viral-like responses to repeat RNAs provide a mechanism for modulation of cellular plasticity in diverse cell types in the PDAC microenvironment.

KW - cancer-associated fibroblast

KW - cellular plasticity

KW - extracellular vesicles

KW - pancreatic cancer

KW - repeat RNA

UR - http://www.scopus.com/inward/record.url?scp=85207757731&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2024.09.024

DO - 10.1016/j.cell.2024.09.024

M3 - Article

C2 - 39383862

AN - SCOPUS:85207757731

SN - 0092-8674

VL - 187

SP - 7232-7247.e23

JO - Cell

JF - Cell

IS - 25

ER -

Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer

Abstract

Keywords

Access to Document

Fingerprint

Cite this