Single-cell transcriptome reveals the novel role of T-bet in suppressing the immature NK gene signature.
Animals
Bone Marrow Cells
/ immunology
Cluster Analysis
Forkhead Box Protein O1
/ genetics
Gene Expression Profiling
Gene Expression Regulation
Genotype
Killer Cells, Natural
/ immunology
Machine Learning
Mechanistic Target of Rapamycin Complex 2
/ deficiency
Mice, Inbred C57BL
Mice, Knockout
Phenotype
Proto-Oncogene Proteins c-akt
/ genetics
RNA-Seq
Rapamycin-Insensitive Companion of mTOR Protein
/ deficiency
Regulatory-Associated Protein of mTOR
/ deficiency
Single-Cell Analysis
T-Box Domain Proteins
/ genetics
Transcriptome
NK cell
T-bet
development
gene signature
immunology
inflammation
mTORC2
mouse
single-cell RNA-sequencing
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
14 05 2020
14 05 2020
Historique:
received:
25
08
2019
accepted:
08
05
2020
pubmed:
15
5
2020
medline:
16
3
2021
entrez:
15
5
2020
Statut:
epublish
Résumé
The transcriptional activation and repression during NK cell ontology are poorly understood. Here, using single-cell RNA-sequencing, we reveal a novel role for T-bet in suppressing the immature gene signature during murine NK cell development. Based on transcriptome, we identified five distinct NK cell clusters and define their relative developmental maturity in the bone marrow. Transcriptome-based machine-learning classifiers revealed that half of the mTORC2-deficient NK cells belongs to the least mature NK cluster. Mechanistically, loss of mTORC2 results in an increased expression of signature genes representing immature NK cells. Since mTORC2 regulates the expression of T-bet through Akt
Identifiants
pubmed: 32406817
doi: 10.7554/eLife.51339
pii: 51339
pmc: PMC7255804
doi:
pii:
Substances chimiques
Forkhead Box Protein O1
0
Foxo1 protein, mouse
0
Rapamycin-Insensitive Companion of mTOR Protein
0
Regulatory-Associated Protein of mTOR
0
Rptor protein, mouse
0
T-Box Domain Proteins
0
T-box transcription factor TBX21
0
rictor protein, mouse
0
Mechanistic Target of Rapamycin Complex 2
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Banques de données
GEO
['GSE150166', 'GSE77695']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : CA179363
Pays : United States
Organisme : MACC Fund
ID : HRHM Program
Pays : International
Organisme : NIDDK NIH HHS
ID : R01 DK052913
Pays : United States
Organisme : NIH HHS
ID : R01 AI102893
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA204231
Pays : United States
Organisme : Blood Research Institute
ID : Graduate Scholar Award
Pays : International
Organisme : NIH HHS
ID : AI102893
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM080202
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA179363
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI079087
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL130724
Pays : United States
Informations de copyright
© 2020, Yang et al.
Déclaration de conflit d'intérêts
CY, JS, RB, YZ, AM, BB, DW, RU, MR, SR, KC, MT, SM No competing interests declared
Références
Nature. 1999 Feb 25;397(6721):702-6
pubmed: 10067894
J Exp Med. 2014 Apr 7;211(4):635-42
pubmed: 24663216
Gigascience. 2018 Jul 1;7(7):
pubmed: 30010766
Cold Spring Harb Perspect Med. 2014 Jan 01;4(1):a014357
pubmed: 24384812
J Exp Med. 2009 Dec 21;206(13):2977-86
pubmed: 19995955
Nat Immunol. 2009 Oct;10(10):1118-24
pubmed: 19749763
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
Immunity. 2004 Apr;20(4):477-94
pubmed: 15084276
J Immunol. 2016 Feb 15;196(4):1753-67
pubmed: 26773150
Nat Rev Immunol. 2011 Aug 26;11(10):645-57
pubmed: 21869816
Nat Immunol. 2002 Jun;3(6):523-8
pubmed: 12006976
J Immunol. 2006 Feb 1;176(3):1517-24
pubmed: 16424180
Cell. 2014 Apr 10;157(2):340-356
pubmed: 24725403
J Immunol. 2001 Aug 1;167(3):1141-4
pubmed: 11466327
Cell. 2016 May 19;165(5):1120-1133
pubmed: 27156451
J Exp Med. 2015 Feb 9;212(2):253-65
pubmed: 25624444
Eur J Immunol. 2000 Jul;30(7):2074-82
pubmed: 10940897
Immunity. 2015 Mar 17;42(3):457-70
pubmed: 25769609
Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18324-9
pubmed: 22021440
Science. 2018 Mar 30;359(6383):1537-1542
pubmed: 29599246
Genome Biol. 2014;15(12):550
pubmed: 25516281
Bioinformatics. 2011 Jun 15;27(12):1739-40
pubmed: 21546393
J Immunol. 1992 Sep 15;149(6):1876-80
pubmed: 1387664
Immunity. 2018 Nov 20;49(5):971-986.e5
pubmed: 30413361
Nat Methods. 2017 Oct;14(10):979-982
pubmed: 28825705
Elife. 2018 May 29;7:
pubmed: 29809146
Mol Aspects Med. 2018 Feb;59:114-122
pubmed: 28712804
J Exp Med. 2015 Nov 16;212(12):2015-25
pubmed: 26503444
Eur J Immunol. 2001 Jun;31(6):1900-9
pubmed: 11433387
Blood. 2001 May 1;97(9):2625-32
pubmed: 11313251
Bioinformatics. 2010 Jul 15;26(14):1752-8
pubmed: 20505004
F1000Res. 2015 Dec 30;4:1521
pubmed: 26925227
Immunity. 1998 Oct;9(4):555-63
pubmed: 9806641
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Nat Rev Cancer. 2009 Nov;9(11):785-97
pubmed: 19851314
Blood. 2011 May 19;117(20):5449-52
pubmed: 21422472
Nucleic Acids Res. 2018 Jan 4;46(D1):D762-D769
pubmed: 29106570
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
J Exp Med. 2007 May 14;204(5):1119-30
pubmed: 17452521
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Nat Immunol. 2015 Mar;16(3):306-17
pubmed: 25621825
Adv Immunol. 2011;109:45-85
pubmed: 21569912
Immunity. 2016 Jan 19;44(1):103-115
pubmed: 26795246
J Immunol. 2007 Apr 15;178(8):4764-70
pubmed: 17404256
Curr Opin Immunol. 2013 Apr;25(2):130-8
pubmed: 23490162
Blood. 2009 May 28;113(22):5488-96
pubmed: 19234143
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
Immunity. 2012 Jan 27;36(1):55-67
pubmed: 22261438
Genome Biol. 2015 Dec 10;16:278
pubmed: 26653891
Nat Immunol. 2008 May;9(5):503-10
pubmed: 18425107
Blood. 2011 Nov 17;118(20):5439-47
pubmed: 21931117
Elife. 2020 May 14;9:
pubmed: 32406817
Annu Rev Immunol. 2006;24:257-86
pubmed: 16551250