Tetraspanin CD82 drives acute myeloid leukemia chemoresistance by modulating protein kinase C alpha and β1 integrin activation.
Adult
Aged
Daunorubicin
/ adverse effects
Drug Resistance, Neoplasm
/ genetics
Female
Gene Expression Regulation, Neoplastic
/ drug effects
HL-60 Cells
Humans
Integrin beta1
/ genetics
Kangai-1 Protein
/ genetics
Leukemia, Myeloid, Acute
/ drug therapy
Male
Middle Aged
Protein Kinase C-alpha
/ genetics
RNA-Seq
p38 Mitogen-Activated Protein Kinases
/ genetics
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
20
11
2019
accepted:
05
03
2020
revised:
03
03
2020
pubmed:
24
3
2020
medline:
26
11
2020
entrez:
24
3
2020
Statut:
ppublish
Résumé
A principal challenge in treating acute myeloid leukemia (AML) is chemotherapy refractory disease. As such, there remains a critical need to identify key regulators of chemotherapy resistance in AML. In this study, we demonstrate that the membrane scaffold, CD82, contributes to the chemoresistant phenotype of AML. Using an RNA-seq approach, we identified the increased expression of the tetraspanin family member, CD82, in response to the chemotherapeutic, daunorubicin. Analysis of the TARGET and BEAT AML databases identifies a correlation between CD82 expression and overall survival of AML patients. Moreover, using a combination of cell lines and patient samples, we find that CD82 overexpression results in significantly reduced cell death in response to chemotherapy. Investigation of the mechanism by which CD82 promotes AML survival in response to chemotherapy identified a crucial role for enhanced protein kinase c alpha (PKCα) signaling and downstream activation of the β1 integrin. In addition, analysis of β1 integrin clustering by super-resolution imaging demonstrates that CD82 expression promotes the formation of dense β1 integrin membrane clusters. Lastly, evaluation of survival signaling following daunorubicin treatment identified robust activation of p38 mitogen-activated protein kinase (MAPK) downstream of PKCα and β1 integrin signaling when CD82 is overexpressed. Together, these data propose a mechanism where CD82 promotes chemoresistance by increasing PKCα activation and downstream activation/clustering of β1 integrin, leading to AML cell survival via activation of p38 MAPK. These observations suggest that the CD82-PKCα signaling axis may be a potential therapeutic target for attenuating chemoresistance signaling in AML.
Identifiants
pubmed: 32203165
doi: 10.1038/s41388-020-1261-0
pii: 10.1038/s41388-020-1261-0
pmc: PMC7210072
mid: NIHMS1572780
doi:
Substances chimiques
CD82 protein, human
0
Integrin beta1
0
Kangai-1 Protein
0
PRKCA protein, human
EC 2.7.11.13
Protein Kinase C-alpha
EC 2.7.11.13
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Daunorubicin
ZS7284E0ZP
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
3910-3925Subventions
Organisme : NCI NIH HHS
ID : P30 CA118100
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL124977
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM085273
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007736
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL122483
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA232480
Pays : United States
Références
American Cancer Society. Cancer facts & figures. Atlanta, GA: American Cancer Society.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.
pubmed: 27069254
doi: 10.1182/blood-2016-03-643544
Nasir SS, Giri S, Nunnery S, Martin MG. Outcome of adolescents and young adults compared with pediatric patients with acute myeloid and promyelocytic leukemia. Clin Lymphoma Myeloma Leuk. 2017;17:126–32. e1.
pubmed: 27836483
doi: 10.1016/j.clml.2016.09.011
Veuger M, Honders W, Spoelder N, Willemze R, Barge R. Effects of the use of multiple cytotoxic drugs on resistance mechanisms in acute myeloid leukemia. Leukemia. 2001;15:503.
doi: 10.1038/sj.leu.2402229
Zhang J, Gu Y, Chen BA. Mechanisms of drug resistance in acute myeloid leukemia. Oncotargets Ther. 2019;12:1937–45.
doi: 10.2147/OTT.S191621
Cloos J, Goemans BF, Hess CJ, van Oostveen JW, Waisfisz Q, Corthals S, et al. Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples. Leukemia. 2006;20:1217–20.
pubmed: 16642044
doi: 10.1038/sj.leu.2404246
El Fakih R, Rasheed W, Hawsawi Y, Alsermani M, Hassanein M. Targeting FLT3 mutations in acute myeloid leukemia. Cells. 2018;7:E4.
pubmed: 29316714
doi: 10.3390/cells7010004
Cook AM, Li L, Ho YW, Lin A, Li L, Stein A, et al. Role of altered growth factor receptor-mediated JAK2 signaling in growth and maintenance of human acute myeloid leukemia stem cells. Blood. 2014;123:2826–37.
pubmed: 24668492
pmcid: 4007609
doi: 10.1182/blood-2013-05-505735
McCubrey JA, Steelman LS, Abrams SL, Bertrand FE, Ludwig DE, Basecke J, et al. Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy. Leukemia. 2008;22:708–22.
pubmed: 18337766
doi: 10.1038/leu.2008.27
Bosman MC, Schuringa JJ, Vellenga E. Constitutive NF-kappaB activation in AML: causes and treatment strategies. Crit Rev Oncol Hematol. 2016;98:35–44.
pubmed: 26490297
doi: 10.1016/j.critrevonc.2015.10.001
Davoudi Z, Akbarzadeh A, Rahmatiyamchi M, Movassaghpour AA, Alipour M, Nejati-Koshki K, et al. Molecular target therapy of AKT and NF-kB signaling pathways and multidrug resistance by specific cell penetrating inhibitor peptides in HL-60 cells. Asian Pac J Cancer Prev. 2014;15:4353–8.
pubmed: 24935396
doi: 10.7314/APJCP.2014.15.10.4353
Hemler ME. Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Bio. 2005;6:801–11.
doi: 10.1038/nrm1736
Hemler ME. Tetraspanin proteins promote multiple cancer stages. Nat Rev Cancer. 2014;14:49–60.
pubmed: 24505619
doi: 10.1038/nrc3640
Kwon HY, Bajaj J, Ito T, Blevins A, Konuma T, Weeks J, et al. Tetraspanin 3 is required for the development and propagation of acute myelogenous leukemia. Cell Stem Cell. 2015;17:152–64.
pubmed: 26212080
pmcid: 4664079
doi: 10.1016/j.stem.2015.06.006
Boyer T, Guihard S, Roumier C, Peyrouze P, Gonzales F, Berthon C, et al. Tetraspanin CD81 is an adverse prognostic marker in acute myeloid leukemia. Oncotarget. 2016;7:62377–85.
pubmed: 27566555
pmcid: 5308734
doi: 10.18632/oncotarget.11481
Burchert A, Notter M, Menssen HD, Schwartz S, Knauf W, Neubauer A, et al. CD82 (KAI1), a member of the tetraspan family, is expressed on early haemopoietic progenitor cells and up-regulated in distinct human leukaemias. Brit J Haematol. 1999;107:494–504.
doi: 10.1046/j.1365-2141.1999.01741.x
Saito-Reis CA, Marjon KD, Pascetti EM, Floren M, Gillette JM. The tetraspanin CD82 regulates bone marrow homing and engraftment of hematopoietic stem and progenitor cells. Mol Biol Cell. 2018;29:2946–58.
pubmed: 30133344
pmcid: 6329911
doi: 10.1091/mbc.E18-05-0305
Nishioka C, Ikezoe T, Yang J, Yokoyama A. Tetraspanin family member, CD82, regulates expression of EZH2 via inactivation of p38 MAPK signaling in leukemia cells. PLoS ONE. 2015;10:e0125017.
pubmed: 25955299
pmcid: 4425466
doi: 10.1371/journal.pone.0125017
Marjon KD, Termini CM, Karlen KL, Saito-Reis C, Soria CE, Lidke KA, et al. Tetraspanin CD82 regulates bone marrow homing of acute myeloid leukemia by modulating the molecular organization of N-cadherin. Oncogene. 2016;35:4132–40.
pubmed: 26592446
doi: 10.1038/onc.2015.449
Termini CM, Lidke KA, Gillette JM. Tetraspanin CD82 regulates the spatiotemporal dynamics of PKC alpha in acute myeloid leukemia. Sci Rep. 2016;29895.
Kurinna S, Konopleva M, Palla SL, Chen W, Kornblau S, Contractor R, et al. Bcl2 phosphorylation and active PKC alpha are associated with poor survival in AML. Leukemia. 2006;20:1316–9.
pubmed: 16642043
doi: 10.1038/sj.leu.2404248
Ruvolo PP, Zhou LR, Watt JC, Ruvolo VR, Burks JK, Jiffar T, et al. Targeting pkc-mediated signal transduction pathways using enzastaurin to promote apoptosis in acute myeloid leukemia-derived cell lines and blast cells. J Cell Biochem. 2011;112:1696–707.
pubmed: 21360576
pmcid: 3394435
doi: 10.1002/jcb.23090
Wakui M, Kuriyama K, Miyazaki Y, Hata T, Taniwaki M, Ohtake S, et al. Diagnosis of acute myeloid leukemia according to the WHO classification in the Japan Adult Leukemia Study Group AML-97 protocol. Int J Hematol. 2008;87:144–51.
pubmed: 18256787
pmcid: 2276241
doi: 10.1007/s12185-008-0025-3
Walter RB, Othus M, Burnett AK, Lowenberg B, Kantarjian HM, Ossenkoppele GJ, et al. Significance of FAB subclassification of “acute myeloid leukemia, NOS” in the 2008 WHO classification: analysis of 5848 newly diagnosed patients. Blood. 2013;121:2424–31.
pubmed: 23325837
pmcid: 3612855
doi: 10.1182/blood-2012-10-462440
Byun JM, Kim YJ, Yoon HJ, Kim SY, Kim HJ, Yoon J, et al. Cytogenetic profiles of 2806 patients with acute myeloid leukemia-a retrospective multicenter nationwide study. Ann Hematol. 2016;95:1223–32.
pubmed: 27230620
doi: 10.1007/s00277-016-2691-1
Okamoto Y, Kudo K, Tabuchi K, Tomizawa D, Taga T, Goto H, et al. Hematopoietic stem-cell transplantation in children with refractory acute myeloid leukemia. Bone Marrow Transpl. 2019;54:1489–98.
doi: 10.1038/s41409-019-0461-0
Takami M, Katayama K, Noguchi K, Sugimoto Y. Protein kinase C alpha-mediated phosphorylation of PIM-1L promotes the survival and proliferation of acute myeloid leukemia cells. Biochem Biophys Res Commun. 2018;503:1364–71.
pubmed: 30017192
doi: 10.1016/j.bbrc.2018.07.049
Efimova T, Deucher A, Kuroki T, Ohba M, Eckert RL. Novel protein kinase C isoforms regulate human keratinocyte differentiation by activating a p38 delta mitogen-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha. J Biol Chem. 2002;277:31753–60.
pubmed: 12080077
doi: 10.1074/jbc.M205098200
Hocevar BA, Morrow DM, Tykocinski ML, Fields AP. Protein kinase C isotypes in human erythroleukemia cell proliferation and differentiation. J Cell Sci. 1992;101:671–9.
pubmed: 1522149
Myklebust JH, Smeland EB, Josefsen D, Sioud M. Protein kinase C-alpha isoform is involved in erythropoietin-induced erythroid differentiation of CD34(+) progenitor cells from human bone marrow. Blood. 2000;95:510–8.
pubmed: 10627456
doi: 10.1182/blood.V95.2.510
Jin JK, Tien PC, Cheng CJ, Song JH, Huang C, Lin SH, et al. Talin1 phosphorylation activates beta1 integrins: a novel mechanism to promote prostate cancer bone metastasis. Oncogene. 2015;34:1811–21.
pubmed: 24793790
doi: 10.1038/onc.2014.116
Ramirez P, Rettig MP, Uy GL, Deych E, Holt MS, Ritchey JK, et al. BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells. Blood. 2009;114:1340–3.
pubmed: 19571319
pmcid: 2727418
doi: 10.1182/blood-2008-10-184721
van Kooyk Y, Figdor CG. Avidity regulation of integrins: the driving force in leukocyte adhesion. Curr Opin Cell Biol. 2000;12:542–7.
pubmed: 10978887
doi: 10.1016/S0955-0674(00)00129-0
Kolanus W, Seed B. Integrins and inside-out signal transduction: converging signals from PKC and PIP3. Curr Opin Cell Biol. 1997;9:725–31.
pubmed: 9330877
doi: 10.1016/S0955-0674(97)80127-5
Martin Ester H-PK, Jorg Sander, Xiaowei Xu. A density-based algorithm for discovering clusters in large spatial databases with noise. In Proceedings of the 2nd International Conference on Knowledge Discovery and Data Mining (KDD-96). Portland, Oregon: AAAI Press; 1996. p. 226–31.
Thornton TM, Rincon M. Non-classical p38 map kinase functions: cell cycle checkpoints and survival. Int J Biol Sci. 2009;5:44–51.
pubmed: 19159010
doi: 10.7150/ijbs.5.44
Wood CD, Thornton TM, Sabio G, Davis RA, Rincon M. Nuclear localization of p38 MAPK in response to DNA damage. Int J Biol Sci. 2009;5:428–37.
pubmed: 19564926
pmcid: 2702826
doi: 10.7150/ijbs.5.428
Gupta J, Igea A, Papaioannou M, Lopez-Casas PP, Llonch E, Hidalgo M, et al. Pharmacological inhibition of p38 MAPK reduces tumor growth in patient-derived xenografts from colon tumors. Oncotarget. 2015;6:8539–51.
pubmed: 25890501
pmcid: 4496165
Naci D, Aoudjit F. Alpha2beta1 integrin promotes T cell survival and migration through the concomitant activation of ERK/Mcl-1 and p38 MAPK pathways. Cell Signal. 2014;26:2008–15.
pubmed: 24880062
doi: 10.1016/j.cellsig.2014.05.016
Scott MJ, Billiar TR. Beta2-integrin-induced p38 MAPK activation is a key mediator in the CD14/TLR4/MD2-dependent uptake of lipopolysaccharide by hepatocytes. J Biol Chem. 2008;283:29433–46.
pubmed: 18701460
pmcid: 2570897
doi: 10.1074/jbc.M803905200
Hwang S, Takimoto T, Hemler ME. Integrin-independent support of cancer drug resistance by tetraspanin CD151. Cell Mol Life Sci. 2019;76:1595–604.
pubmed: 30778617
pmcid: 6439156
doi: 10.1007/s00018-019-03014-7
Ye M, Wei T, Wang Q, Sun Y, Tang R, Guo L, et al. TSPAN12 promotes chemoresistance and proliferation of SCLC under the regulation of miR-495. Biochem Biophys Res Commun. 2017;486:349–56.
pubmed: 28302484
doi: 10.1016/j.bbrc.2017.03.044
Kohmo S, Kijima T, Otani Y, Mori M, Minami T, Takahashi R, et al. Cell surface tetraspanin CD9 mediates chemoresistance in small cell lung cancer. Cancer Res. 2010;70:8025–35.
pubmed: 20940407
doi: 10.1158/0008-5472.CAN-10-0996
Ullah M, Akbar A, Ng NN, Concepcion W, Thakor AS. Mesenchymal stem cells confer chemoresistance in breast cancer via a CD9 dependent mechanism. Oncotarget. 2019;10:3435–50.
pubmed: 31191817
pmcid: 6544397
Nishioka C, Ikezoe T, Yang J, Nobumoto A, Kataoka S, Tsuda M, et al. CD82 regulates STAT5/IL-10 and supports survival of acute myelogenous leukemia cells. Int J Cancer. 2014;134:55–64.
pubmed: 23797738
doi: 10.1002/ijc.28348
Ji H, Chen L, Xing Y, Li S, Dai J, Zhao P, et al. CD82 supports survival of childhood acute myeloid leukemia cells via activation of Wnt/beta-catenin signaling pathway. Pediatr Res. 2019;85:1024–31.
pubmed: 30862962
doi: 10.1038/s41390-019-0370-3
Nishioka C, Ikezoe T, Takeuchi A, Nobumoto A, Tsuda M, Yokoyama A. The novel function of CD82 and its impact on BCL2L12 via AKT/STAT5 signal pathway in acute myelogenous leukemia cells. Leukemia. 2015;29:2296–306.
pubmed: 26260387
doi: 10.1038/leu.2015.219
Bonardi F, Fusetti F, Deelen P, van Gosliga D, Vellenga E, Schuringa JJ. A proteomics and transcriptomics approach to identify leukemic stem cell (LSC) markers. Mol Cell Proteom. 2013;12:626–37.
doi: 10.1074/mcp.M112.021931
Tonoli H, Barrett JC. CD82 metastasis suppressor gene: a potential target for new therapeutics? Trends Mol Med. 2005;11:563–70.
pubmed: 16271511
doi: 10.1016/j.molmed.2005.10.002
Miranti CK. Controlling cell surface dynamics and signaling: how CD82/KAI1 suppresses metastasis. Cell Signal 2009;21:196–211.
pubmed: 18822372
doi: 10.1016/j.cellsig.2008.08.023
Tsai YC, Weissman AM. Dissecting the diverse functions of the metastasis suppressor CD82/KAI1. FEBS Lett. 2011;585:3166–73.
pubmed: 21875585
pmcid: 3409691
doi: 10.1016/j.febslet.2011.08.031
Nishioka C, Ikezoe T, Furihata M, Yang J, Serada S, Naka T, et al. CD34+/CD38 acute myelogenous leukemia cells aberrantly express CD82 which regulates adhesion and survival of leukemia stem cells. Int J Cancer. 2013;132:2006–19.
pubmed: 23055153
doi: 10.1002/ijc.27904
Brockstein B, Samuels B, Humerickhouse R, Arietta R, Fishkin P, Wade J. et al. Phase II studies of bryostatin-1 in patients with advanced sarcoma and advanced head and neck cancer. Invest New Drugs. 2001;19:249–54.
pubmed: 11561683
doi: 10.1023/A:1010628903248
Varterasian ML, Mohammad RM, Shurafa MS, Hulburd K, Pemberton PA, Rodriguez DH, et al. Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Clin Cancer Res. 2000;6:825–8.
pubmed: 10741703
Crump M, Leppa S, Fayad L, Lee JJ, Di Rocco A, Ogura M, et al. Randomized, double-blind, phase III trial of enzastaurin versus placebo in patients achieving remission after first-line therapy for high-risk diffuse large b-cell lymphoma. J Clin Oncol. 2016;34:2484–92.
pubmed: 27217449
doi: 10.1200/JCO.2015.65.7171
Aoudjit F, Vuori K. Integrin signaling in cancer cell survival and chemoresistance. Chemother Res Pract. 2012;2012:283181.
pubmed: 22567280
pmcid: 3332161
Naci D, El Azreq MA, Chetoui N, Lauden L, Sigaux F, Charron D, et al. alpha2beta1 integrin promotes chemoresistance against doxorubicin in cancer cells through extracellular signal-regulated kinase (ERK). J Biol Chem. 2012;287:17065–76.
pubmed: 22457358
pmcid: 3366820
doi: 10.1074/jbc.M112.349365
Nair MG, Desai K, Prabhu JS, Hari PS, Remacle J, Sridhar TS. beta3 integrin promotes chemoresistance to epirubicin in MDA-MB-231 through repression of the pro-apoptotic protein, BAD. Exp Cell Res. 2016;346:137–45.
pubmed: 27235542
doi: 10.1016/j.yexcr.2016.05.015
Sansing HA, Sarkeshik A, Yates JR, Patel V, Gutkind JS, Yamada KM, et al. Integrin alphabeta1, alphavbeta, alpha6beta effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance. Biochem Biophys Res Commun. 2011;406:171–6.
pubmed: 21291860
pmcid: 3102534
doi: 10.1016/j.bbrc.2011.01.109
Seguin L, Desgrosellier JS, Weis SM, Cheresh DA. Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance. Trends Cell Biol. 2015;25:234–40.
pubmed: 25572304
pmcid: 4380531
doi: 10.1016/j.tcb.2014.12.006
Berrazouane S, Boisvert M, Salti S, Mourad W, Al-Daccak R, Barabe F, et al. Beta1 integrin blockade overcomes doxorubicin resistance in human T-cell acute lymphoblastic leukemia. Cell Death Dis. 2019;10:357.
pubmed: 31043590
pmcid: 6494825
doi: 10.1038/s41419-019-1593-2
Zhang XA, Bontrager AL, Hemler ME. Transmembrane-4 superfamily proteins associate with activated protein kinase C (PKC) and link PKC to specific beta(1) integrins. J Biol Chem. 2001;276:25005–13.
pubmed: 11325968
doi: 10.1074/jbc.M102156200
Termini CM, Cotter ML, Marjon KD, Buranda T, Lidke K, Gillette JM. Regulation of VLA-4 mediated hematopoietic stem/progenitor cell adhesion by CD82. Mol Biol Cell. 2012;23:1545–1697.
Bachegowda L, Morrone K, Winski SL, Mantzaris I, Bartenstein M, Ramachandra N, et al. Pexmetinib: a novel dual inhibitor of Tie2 and p38 MAPK with efficacy in preclinical models of myelodysplastic syndromes and acute myeloid leukemia. Cancer Res. 2016;76:4841–9.
pubmed: 27287719
pmcid: 5398415
doi: 10.1158/0008-5472.CAN-15-3062
Garcia-Manero G, Khoury HJ, Jabbour E, Lancet J, Winski SL, Cable L, et al. A phase I study of oral ARRY-614, a p38 MAPK/Tie2 dual inhibitor, in patients with low or intermediate-1 risk myelodysplastic syndromes. Clin Cancer Res. 2015;21:985–94.
pubmed: 25480830
doi: 10.1158/1078-0432.CCR-14-1765
Beckwith KA, Byrd JC, Muthusamy N. Tetraspanins as therapeutic targets in hematological malignancy: a concise review. Front Physiol. 2015;6:91.
pubmed: 25852576
pmcid: 4369647
doi: 10.3389/fphys.2015.00091
Brown RB, Madrid NJ, Suzuki H, Ness SA. Optimized approach for Ion Proton RNA sequencing reveals details of RNA splicing and editing features of the transcriptome. PLoS ONE. 2017;12:e0176675.
pubmed: 28459821
pmcid: 5411089
doi: 10.1371/journal.pone.0176675
Brayer KJ, Frerich CA, Kang H, Ness SA. Recurrent fusions in MYB and MYBL1 define a common, transcription factor-driven oncogenic pathway in salivary gland adenoid cystic carcinoma. Cancer Discov. 2016;6:176–87.
pubmed: 26631070
doi: 10.1158/2159-8290.CD-15-0859
Frerich CA, Brayer KJ, Painter BM, Kang H, Mitani Y, El-Naggar AK, et al. Transcriptomes define distinct subgroups of salivary gland adenoid cystic carcinoma with different driver mutations and outcomes. Oncotarget. 2018;9:7341–58.
pubmed: 29484115
doi: 10.18632/oncotarget.23641
Anders S, Pyl PT, Huber W. HTSeq-a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31:166–9.
pubmed: 25260700
doi: 10.1093/bioinformatics/btu638
Robinson MD, McCarthy DJ, Smyth GK. edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26:139–40.
pubmed: 19910308
doi: 10.1093/bioinformatics/btp616
Varet H, Brillet-Gueguen L, Coppee JY, Dillies MA. SARTools: a DESeq2- and EdgeR-based R pipeline for comprehensive differential analysis of RNA-Seq data. PLoS ONE. 2016;11:e0157022.
pubmed: 27280887
pmcid: 4900645
doi: 10.1371/journal.pone.0157022
Saldanha AJ. Java treeview-extensible visualization of microarray data. Bioinformatics. 2004;20:3246–8.
pubmed: 15180930
doi: 10.1093/bioinformatics/bth349
Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun. 2019;10:1523.
pubmed: 30944313
pmcid: 6447622
doi: 10.1038/s41467-019-09234-6
Tyner JW, Tognon CE, Bottomly D, Wilmot B, Kurtz SE, Druker BJ, et al. Functional genomic landscape of acute myeloid leukaemia. Nature. 2018;562:526–31.
pubmed: 30333627
pmcid: 6280667
doi: 10.1038/s41586-018-0623-z
Valley CC, Liu S, Lidke DS, Lidke KA. Sequential superresolution imaging of multiple targets using a single fluorophore. PLoS ONE. 2015;10:e0123941.
pubmed: 25860558
pmcid: 4393115
doi: 10.1371/journal.pone.0123941
Huang F, Schwartz SL, Byars JM, Lidke KA. Simultaneous multiple-emitter fitting for single molecule super-resolution imaging. Biomed Opt Express. 2011;2:1377–93.
pubmed: 21559149
pmcid: 3087594
doi: 10.1364/BOE.2.001377