Establishment of a reference single-cell RNA sequencing dataset for human pancreatic adenocarcinoma.

Cancer Cancer systems biology Transcriptomics

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
19 Aug 2022
Historique:
received: 02 03 2022
revised: 14 05 2022
accepted: 17 06 2022
entrez: 18 7 2022
pubmed: 19 7 2022
medline: 19 7 2022
Statut: epublish

Résumé

Single-cell RNA sequencing (scRNAseq) has been used to assess the intra-tumor heterogeneity and microenvironment of pancreatic ductal adenocarcinoma (PDAC). However, previous knowledge is not fully universalized. Here, we built a single cell atlas of PDAC from six datasets containing over 70 samples and >130,000 cells, and demonstrated its application to the reanalysis of the previous bulk transcriptomic cohorts and inferring cell-cell communications. The cell decomposition of bulk transcriptomics using scRNAseq data showed the cellular heterogeneity of PDAC; moreover, high levels of tumor cells and fibroblasts were indicative of poor-prognosis. Refined tumor subtypes signature indicated the tumor cell dynamics in intra-tumor and their specific regulatory network. We further identified functionally distinct tumor clusters that had close interaction with fibroblast subtypes via different signaling pathways dependent on subtypes. Our analysis provided a reference dataset for PDAC and showed its utility in research on the microenvironment of intra-tumor heterogeneity.

Identifiants

pubmed: 35847558
doi: 10.1016/j.isci.2022.104659
pii: S2589-0042(22)00931-2
pmc: PMC9283889
doi:

Types de publication

Journal Article

Langues

eng

Pagination

104659

Informations de copyright

© 2022 The Author(s).

Déclaration de conflit d'intérêts

Partial institutional endowments were received from Taiho Pharmaceutical Co., Ltd. (Tokyo, Japan), Hirotsu Bio Science Inc. (Tokyo, Japan), Kinshu-kai Medical Corporation (Osaka, Japan), Kyowa-kai Medical Corporation (Osaka, Japan), IDEA Consultants Inc. (Tokyo, Japan), and Unitech Co. Ltd. (Chiba, Japan).

Références

Front Immunol. 2019 May 22;10:1078
pubmed: 31231358
Nat Methods. 2017 Nov;14(11):1083-1086
pubmed: 28991892
Nat Commun. 2021 Feb 17;12(1):1088
pubmed: 33597522
Nat Genet. 2015 Oct;47(10):1168-78
pubmed: 26343385
Mol Biosyst. 2016 Feb;12(2):477-9
pubmed: 26661513
Cancer Res. 2019 Oct 15;79(20):5367-5381
pubmed: 31439548
Clin Cancer Res. 2021 Nov 1;27(21):5912-5921
pubmed: 34426439
Front Cell Dev Biol. 2021 Nov 05;9:743908
pubmed: 34805152
Bioinformatics. 2019 Jul 15;35(14):i436-i445
pubmed: 31510660
Sci Rep. 2020 Jan 15;10(1):337
pubmed: 31941932
Nat Commun. 2019 Oct 18;10(1):4729
pubmed: 31628300
Cell Rep. 2021 Apr 13;35(2):108990
pubmed: 33852841
Cancer Res. 2010 Mar 1;70(5):2115-25
pubmed: 20160041
Innovation (Camb). 2021 Jul 01;2(3):100141
pubmed: 34557778
Trends Cancer. 2018 Jun;4(6):418-428
pubmed: 29860986
Proc Natl Acad Sci U S A. 2017 Jan 17;114(3):E406-E415
pubmed: 28049845
STAR Protoc. 2020 Aug 04;1(2):100079
pubmed: 33111113
Nature. 2020 May;581(7808):303-309
pubmed: 32214235
Trends Genet. 2017 Dec;33(12):943-959
pubmed: 28919019
Nat Methods. 2020 Feb;17(2):159-162
pubmed: 31819264
J Gastrointest Oncol. 2018 Dec;9(6):1005-1013
pubmed: 30603119
Cell Syst. 2016 Oct 26;3(4):346-360.e4
pubmed: 27667365
Gut. 2022 Apr;71(4):766-777
pubmed: 33846140
J Exp Med. 2017 Mar 6;214(3):579-596
pubmed: 28232471
Sci Rep. 2021 Jun 4;11(1):11842
pubmed: 34088917
Clin Cancer Res. 2020 Sep 15;26(18):4901-4910
pubmed: 32156747
Nat Genet. 2020 Feb;52(2):231-240
pubmed: 31932696
Nat Methods. 2015 May;12(5):453-7
pubmed: 25822800
CA Cancer J Clin. 2020 Jan;70(1):7-30
pubmed: 31912902
Cancer Discov. 2019 Aug;9(8):1102-1123
pubmed: 31197017
Gastroenterology. 2021 Mar;160(4):1330-1344.e11
pubmed: 33212097
Front Immunol. 2018 Aug 15;9:1878
pubmed: 30158932
Nat Rev Gastroenterol Hepatol. 2021 Jul;18(7):451-452
pubmed: 34040169
Cancers (Basel). 2018 Jan 12;10(1):
pubmed: 29329208
Bioinformatics. 2018 Sep 1;34(17):i884-i890
pubmed: 30423086
Cell. 2021 Jun 24;184(13):3573-3587.e29
pubmed: 34062119
Clin Cancer Res. 2020 Jan 1;26(1):82-92
pubmed: 31754050
Nature. 2016 Mar 3;531(7592):47-52
pubmed: 26909576
Nucleic Acids Res. 2019 Jul 2;47(W1):W556-W560
pubmed: 31114875
Nat Commun. 2020 Sep 9;11(1):4516
pubmed: 32908137
Cancer Discov. 2020 Feb;10(2):232-253
pubmed: 31699795
Nature. 2020 Nov;587(7834):477-482
pubmed: 33116311
PLoS One. 2018 Aug 24;13(8):e0202449
pubmed: 30142155
Nat Commun. 2020 Apr 24;11(1):1971
pubmed: 32332754
BMC Bioinformatics. 2011 Aug 04;12:323
pubmed: 21816040
Gastroenterology. 2019 May;156(7):2056-2072
pubmed: 30660727
Cancer Res. 2021 Aug 15;81(16):4305-4318
pubmed: 34049975
J Cell Biochem. 2017 Aug;118(8):2026-2036
pubmed: 27791279
Saudi J Gastroenterol. 2019 Jan-Feb;25(1):3-13
pubmed: 30588953
Proc Natl Acad Sci U S A. 2020 May 19;117(20):10876-10887
pubmed: 32354994
Nat Biotechnol. 2020 Mar;38(3):333-342
pubmed: 31932730
Nat Med. 2011 Apr;17(4):500-3
pubmed: 21460848
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Front Cell Dev Biol. 2021 Jul 15;9:655152
pubmed: 34336821
Cell. 2021 Oct 14;184(21):5482-5496.e28
pubmed: 34597583
Cell Res. 2019 Sep;29(9):725-738
pubmed: 31273297
Ann Oncol. 2019 Sep 1;30(9):1428-1436
pubmed: 31161208
Life Sci Alliance. 2021 Mar 29;4(6):
pubmed: 33782087
Nucleic Acids Res. 2016 May 5;44(8):e71
pubmed: 26704973
Cancer Cell. 2017 Aug 14;32(2):185-203.e13
pubmed: 28810144
Mol Oncol. 2015 Feb;9(2):355-64
pubmed: 25300573
World J Gastroenterol. 2018 Nov 21;24(43):4846-4861
pubmed: 30487695
Cell. 2017 Aug 24;170(5):875-888.e20
pubmed: 28757253
Nat Cancer. 2020 Nov;1(11):1097-1112
pubmed: 34296197
EBioMedicine. 2021 Apr;66:103315
pubmed: 33819739
Science. 2016 Apr 8;352(6282):189-96
pubmed: 27124452
Cell. 2021 Dec 9;184(25):6119-6137.e26
pubmed: 34890551
Cancer Cell. 2021 Oct 11;39(10):1422-1437.e10
pubmed: 34597589
Gut. 2017 Sep;66(9):1665-1676
pubmed: 27325420
Sci Adv. 2020 Jul 22;6(30):eaba2619
pubmed: 32832661
Genome Med. 2020 Sep 29;12(1):80
pubmed: 32988401
Bioinformatics. 2015 Feb 15;31(4):608-9
pubmed: 25677125
J Clin Med. 2021 Jan 04;10(1):
pubmed: 33406790

Auteurs

Ryota Chijimatsu (R)

Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
Center for Comprehensive Genomic Medicine, Okayama University Hospital, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.

Shogo Kobayashi (S)

Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Yu Takeda (Y)

Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Masatoshi Kitakaze (M)

Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Shotaro Tatekawa (S)

Department of Radiation Oncology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Yasuko Arao (Y)

Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Mika Nakayama (M)

Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Naohiro Tachibana (N)

Department of Orthopaedic Surgery, Section of Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Taku Saito (T)

Department of Orthopaedic Surgery, Section of Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Daisuke Ennishi (D)

Center for Comprehensive Genomic Medicine, Okayama University Hospital, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.

Shuta Tomida (S)

Center for Comprehensive Genomic Medicine, Okayama University Hospital, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.

Kazuki Sasaki (K)

Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Daisaku Yamada (D)

Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Yoshito Tomimaru (Y)

Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Hidenori Takahashi (H)

Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Daisuke Okuzaki (D)

Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.

Daisuke Motooka (D)

Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.

Takahito Ohshiro (T)

SANKEN (The Institute of Scientific and Industrial Research), Osaka University, 8-1 Mihogaoka, Osaka, Ibaraki 567-0047, Japan.

Masateru Taniguchi (M)

SANKEN (The Institute of Scientific and Industrial Research), Osaka University, 8-1 Mihogaoka, Osaka, Ibaraki 567-0047, Japan.

Yutaka Suzuki (Y)

Laboratory of Systems Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwanoha, Kashiwa-shi, Chiba 272-8562, Japan.

Kazuhiko Ogawa (K)

Department of Radiation Oncology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Masaki Mori (M)

Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
Tokai University Graduate School of Medicine, Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

Yuichiro Doki (Y)

Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Hidetoshi Eguchi (H)

Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Hideshi Ishii (H)

Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.

Classifications MeSH