Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 11 2021
11 11 2021
Historique:
received:
19
12
2020
accepted:
20
10
2021
entrez:
12
11
2021
pubmed:
13
11
2021
medline:
25
12
2021
Statut:
epublish
Résumé
Cellular heterogeneity is a major cause of treatment resistance in cancer. Despite recent advances in single-cell genomic and transcriptomic sequencing, it remains difficult to relate measured molecular profiles to the cellular activities underlying cancer. Here, we present an integrated experimental system that connects single cell gene expression to heterogeneous cancer cell growth, metastasis, and treatment response. Our system integrates single cell transcriptome profiling with DNA barcode based clonal tracking in patient-derived xenograft models. We show that leukemia cells exhibiting unique gene expression respond to different chemotherapies in distinct but consistent manners across multiple mice. In addition, we uncover a form of leukemia expansion that is spatially confined to the bone marrow of single anatomical sites and driven by cells with distinct gene expression. Our integrated experimental system can interrogate the molecular and cellular basis of the intratumoral heterogeneity underlying disease progression and treatment resistance.
Identifiants
pubmed: 34764253
doi: 10.1038/s41467-021-26771-1
pii: 10.1038/s41467-021-26771-1
pmc: PMC8586369
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6522Subventions
Organisme : NHLBI NIH HHS
ID : R00 HL113104
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL150826
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014089
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL138414
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197628
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA233412
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA213138
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA157644
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA206463
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL138225
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135292
Pays : United States
Informations de copyright
© 2021. The Author(s).
Références
Nat Rev Cancer. 2017 Aug 24;17(9):557-569
pubmed: 28835719
Nature. 2018 Dec;564(7735):219-224
pubmed: 30518857
Mutat Res. 2005 Oct 15;578(1-2):100-16
pubmed: 16109433
Cancer Res. 2006 Apr 1;66(7):3351-4, discussion 3354
pubmed: 16585151
PLoS One. 2012;7(3):e33894
pubmed: 22479469
Nat Commun. 2014 Dec 23;5:5871
pubmed: 25532760
Cell Rep. 2016 May 24;15(8):1848-57
pubmed: 27184851
Am J Hematol. 1977;3:105-19
pubmed: 602932
Cancer Cell. 2015 Jan 12;27(1):15-26
pubmed: 25584892
Cell. 2015 May 21;161(5):1202-1214
pubmed: 26000488
EMBO Rep. 2018 Aug;19(8):
pubmed: 29848511
Cell. 2016 Sep 22;167(1):260-274.e22
pubmed: 27641504
Cell. 2017 Feb 9;168(4):613-628
pubmed: 28187284
Tumour Biol. 2016 Sep;37(9):12241-12250
pubmed: 27240591
Science. 2013 Feb 1;339(6119):543-8
pubmed: 23239622
Nature. 2020 Jul;583(7817):585-589
pubmed: 32669716
Cancer Res. 2014 Feb 15;74(4):1272-83
pubmed: 24356420
Nature. 2013 Sep 19;501(7467):338-45
pubmed: 24048066
Annu Rev Pathol. 2013 Jan 24;8:277-302
pubmed: 23092187
Cancer Discov. 2014 Sep;4(9):998-1013
pubmed: 25185190
J Exp Med. 2003 Jul 7;198(1):91-8
pubmed: 12835482
Pediatr Int. 2018 Jan;60(1):4-12
pubmed: 29143423
Oncogene. 2019 Jul;38(29):5751-5765
pubmed: 31222103
Immunol Rev. 2016 Mar;270(1):95-112
pubmed: 26864107
Cancer Res. 2003 Nov 15;63(22):7891-9
pubmed: 14633718
Sci Transl Med. 2012 Aug 29;4(149):149ra118
pubmed: 22932223
N Engl J Med. 2012 Mar 8;366(10):883-892
pubmed: 22397650
N Engl J Med. 2008 Mar 13;358(11):1148-59
pubmed: 18337604
J Biol Chem. 2010 May 14;285(20):15088-15099
pubmed: 20220131
Nat Biotechnol. 2011 Oct 02;29(10):928-33
pubmed: 21964413
Front Cell Dev Biol. 2020 Apr 23;8:213
pubmed: 32391354
Cancer Lett. 2015 Jan 28;356(2 Pt B):880-90
pubmed: 25449779
Clin Cancer Res. 2007 Jul 1;13(13):3989-98
pubmed: 17606733
Nat Med. 2015 May;21(5):440-8
pubmed: 25849130
Nat Genet. 2017 Nov;49(11):1567-1575
pubmed: 28991255
Blood. 2011 Aug 25;118(8):2191-9
pubmed: 21715311
Nature. 2017 Sep 7;549(7670):96-100
pubmed: 28854174
Ann Intern Med. 1975 Mar;82(3):365-6
pubmed: 1172924
Cancer Cell. 2016 Apr 11;29(4):440-451
pubmed: 27070699
Blood. 2017 Jun 15;129(24):3210-3220
pubmed: 28396495
Cells. 2019 May 06;8(5):
pubmed: 31064068
Nature. 2020 Nov;587(7834):477-482
pubmed: 33116311
Cell. 2018 May 3;173(4):879-893.e13
pubmed: 29681456
Nat Rev Clin Oncol. 2012 Apr 17;9(6):338-50
pubmed: 22508028
Sci Rep. 2015 Aug 25;5:13006
pubmed: 26302712
Nat Commun. 2019 Feb 15;10(1):766
pubmed: 30770823
Science. 2020 Feb 14;367(6479):
pubmed: 31974159
Nat Rev Clin Oncol. 2018 Feb;15(2):81-94
pubmed: 29115304
Nat Commun. 2020 Mar 27;11(1):1446
pubmed: 32221288
Nature. 2015 Feb 19;518(7539):422-6
pubmed: 25470049
Cancer Res. 2015 Aug 1;75(15):2963-8
pubmed: 26180079
Cell. 2019 Aug 8;178(4):835-849.e21
pubmed: 31327527
Cancer Cell. 2016 Dec 12;30(6):849-862
pubmed: 27916615
Leuk Lymphoma. 2002 Dec;43(12):2331-4
pubmed: 12613520
Nature. 2014 Aug 14;512(7513):155-60
pubmed: 25079324
Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13266-71
pubmed: 16141323
J Biol Chem. 2020 Oct 2;295(40):13737-13752
pubmed: 32709750
Haematologica. 2016 Jul;101(7):e272-6
pubmed: 27036158
Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):17947-52
pubmed: 25425670
Nat Rev Cancer. 2017 Apr;17(4):254-268
pubmed: 28104906
Microsc Res Tech. 2003 Apr 15;60(6):540-51
pubmed: 12645002
Leukemia. 2014 Nov;28(11):2188-96
pubmed: 24699307
Proc Natl Acad Sci U S A. 2019 Jan 22;116(4):1447-1456
pubmed: 30622181
Br J Haematol. 2019 Jun;185(5):836-851
pubmed: 30916375
Nat Protoc. 2020 Apr;15(4):1436-1458
pubmed: 32132718
Nat Commun. 2017 Jan 16;8:14049
pubmed: 28091601
Nature. 2013 Sep 19;501(7467):328-37
pubmed: 24048065
Nature. 2012 Jan 11;481(7382):506-10
pubmed: 22237025
BMC Cancer. 2015 Feb 13;15:53
pubmed: 25884418