RNA M6 A Reader YTHDF2 Tswj NK Cell Antitumor Thiab Antiviral Immunity Part 6

Metastatic melanoma qauv thiab MCMV kev sib tw

B16F10 hlwb (105) tau txhaj iv rau hauv nas. 14 d tom qab txhaj tshuaj, nas tau euthanized rau postmortem tsom xam. Metastatic nodules nyob rau hauv lub ntsws tau soj ntsuam macroscopically thiab suav. B16F10 cell kab yog muab los ntawm Hua Yu (City of Hope, Los Angeles, CA). Ythdf2ΔNK thiab Ythdf2WT nas tau kis tus kab mob ip txhaj tshuaj Smith hom MCMV (2.5 × 104 PFU), uas tau yuav los ntawm American Type Culture Collection (VR-1399). Cov ntshav peripheral tau txais los ntawm submandibular puncture rau hnub 0, 4, thiab 7 tom qab kis kab mob.

Pulmonary metastasis nodules xa mus rau cov nodules tsim los ntawm cov qog nqaij hlav qog nqaij hlav los ntawm lwm qhov chaw uas tsiv mus rau lub ntsws los ntawm cov ntshav los yog lymphatic system. Rau ntau tus neeg mob, qhov no yog ib qho tshwm sim ntawm mob ntsws cancer.

Txawm li cas los xij, txawm hais tias lub ntsws metastasis nodules ua rau muaj kev hem thawj rau cov neeg mob lub cev kev noj qab haus huv, tsis muaj kev sib raug zoo ntawm nws thiab kev nco. Yog li ntawd, peb yuav tsum nquag ntsib cov teeb meem ntawm lub ntsws cancer thiab lub ntsws metastasis nodules, thiab tsis txhob cia cov kev xav tsis zoo thiab kev ntxhov siab cuam tshuam rau peb lub cev thiab lub hlwb.

Tib lub sijhawm, peb tuaj yeem tswj hwm thiab txhim kho kev nco los ntawm qee txoj hauv kev zoo. Piv txwv li, ua qee qhov kev qhia txog kev nco, xws li kev suav lej, nyeem ntawv, mloog suab paj nruag, ua si, thiab lwm yam. Tsis tas li ntawd, ua raws li kev coj noj coj ua zoo, xws li kev tawm dag zog tsis tu ncua, pw tsaug zog txaus, noj zaub mov zoo, thiab lwm yam. txhim kho peb lub cim xeeb.

Qhov tseem ceeb tshaj plaws yog ua kom tus cwj pwm zoo. Txawm hais tias koj ntsib teeb meem dab tsi, koj yuav tsum ntseeg koj lub zog thiab qhov hloov pauv ntawm koj lub paj hlwb, thiab dhau los ntawm kev hloov kho thiab cov lus teb zoo, koj yuav dhau los ua tiav cov teeb meem.

Nyob rau hauv luv luv, txawm hais tias metastatic nodules nyob rau hauv lub ntsws ua rau muaj kev hem thawj rau lub cev noj qab haus huv, lawv tsis ncaj qha ntsig txog kev nco. Peb yuav tsum fim nws zoo thiab tswj thiab txhim kho peb lub cim xeeb los ntawm kev kho peb lub neej thiab tswj tus cwj pwm zoo. Nws tuaj yeem pom tau tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco, vim Cistanche deserticola tseem tuaj yeem tswj hwm qhov sib npaug ntawm cov neurotransmitters, xws li nce qib ntawm acetylcholine thiab kev loj hlob. Cov khoom no tseem ceeb heev rau kev nco thiab kev kawm. Tsis tas li ntawd, Cistanche deserticola tseem tuaj yeem txhim kho cov ntshav khiav thiab txhawb nqa cov pa oxygen, uas tuaj yeem ua kom lub hlwb tau txais cov as-ham txaus thiab lub zog, yog li txhim kho lub hlwb tseem ceeb thiab kev ua siab ntev. Nws tuaj yeem pom tau tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco, vim Cistanche deserticola tseem tuaj yeem tswj hwm qhov sib npaug ntawm cov neurotransmitters, xws li nce qib ntawm acetylcholine thiab kev loj hlob. Cov khoom no tseem ceeb heev rau kev nco thiab kev kawm. Tsis tas li ntawd, Cistanche deserticola tseem tuaj yeem txhim kho cov ntshav khiav thiab txhawb nqa cov pa oxygen, uas tuaj yeem ua kom lub hlwb tau txais cov as-ham txaus thiab lub zog, yog li txhim kho lub hlwb tseem ceeb thiab kev ua siab ntev.

Nyem paub cov tshuaj ntxiv los txhawb kev nco

Tom qab ntsuas cov kab mob hauv cov ntshav peripheral, spleen, thiab siab, DNA raug cais tawm siv QIAGEN DNeasy Blood and Tissue Kitfor qPCR tsom xam. Cov primers hauv qab no tau siv: MCMV-IE1, 59-AGCCACCAACATTGACCACGCAC-39 (rau pem hauv ntej) thiab MCMVIE1, ​​59-GCCCCAACCAGGACACACAACTC-39 (rov qab).

Hauv vivo nas kho nrog IL-15

Rau hauv vivo nas kho nrog IL-15, Ythdf2ΔNK thiab Ythdf2WTmice tau txhaj nrog 2 µg ip recombinant tib neeg IL-15 (cat.no. 745101; National Cancer Institute) rau 5 d. Cov nas kho thiab tswj tau ces euthanized rau kev ntsuas cytometric ntws.

Flow cytometry

Ib leeg-cell raug tshem tawm tau npaj los ntawm BM, ntshav, spleen, siab, thiab ntsws ntawm Ythdf2ΔNK thiab Ythdf2WT nas raws li tau piav ua ntej (Wang li al., 2018b). Flow cytometry analysis thiab cellsorting tau ua tiav ntawm LSRFortessa X-20 thiab FACSAriaFusion Flow Cytometer (BD Biosciences), raws li.

Datawere soj ntsuam siv NovoExpress software (Agilent Technologies).

Cov nram qab no fluorescence dye-labeled antibodies los ntawm BD Biosciences, BioLegend, Invitrogen, los yog Cell Signaling Technology tau siv: CD3ε (145-2C11), CD19 (1D3), Gr-1 (RB6-8C5 ), TER-119 (TER-119), CD11c (N418), CD4 (GK1.5), CD8 ({17}}.7), CD122 (5H4), CD132 (TUGm2), NK1.1 (PK136), CD11b (M1/70), CD27 (LG.3A10), CD117 (2B8), CD127 (SB/199), CD135 (A2F10.1), KLRG1 (2F1), CD45 ({{46) }}F11), CD45.1 (A20), CD45.2 (104), IFN- (XMG1.2), 2B4 (m2B4), granzyme B (QA16A02), perforin (S16009A), Ly49H (3D10), Ly49D ( 4e5), CD69 (H1.2F3), CD226(TX42.1), NKG2D (CX5), NKG2A (16A11), NKp46 (29A1.4), TIGIT(1G9), PD-1 (J43), annexin V, Ki67 (b56), Tbet (4b10), thiab Eomes (WD1928), phospho-p44/42 Erk1/2 (Thr202/Tyr204, #9101), phospho-Akt (Ser473, #5315), phospho-S6 ribosomal protein , phospho-Stat3 (Tyr705, #9145), thiab phospho-Stat5 (Tyr694, #9539).

Rau qhov kev ntsuam xyuas ntawm NK cell proliferation, cov hlwb raug sau nrog 5 µM CTV (Invitrogen) raws li cov chaw tsim khoom cov txheej txheem ua ntej xa lawv mus rau cov neeg txais. Intracellular staining ntawm Ki67, Tbet, thiab Eomes tau ua los ntawm kev kho thiab permeabilizing nrog Foxp3 / Transcription Factor Staining Kit (eBioscience).

Rau kev tshawb nrhiav cov phosphorylated proteins, purified splenic NK hlwb raug pretreated nrog recombinant tib neeg IL-15 (50 ng / ml) rau 1 h thiab ces kho nrog Phosflow Fix Buffer Kuv ua raws li permeabilization nrog Phosflow Perm Buffer III (BD Biosciences) thiab stainingwith tshuaj tiv thaiv.

Kev hloov ntawm tes hloov

Rau kev ntsuam xyuas cov txiaj ntsig ntawm Ythdf2 deficiency ntawm NK cell maturation, sib tov ntawm 5 × 106 BM hlwb ntawm 1: 1 piv los ntawm CD45.1 orYthdf2ΔNK CD45.2 nas tau cotransferred rau hauv Rag2−/-Il2rg-/- nas. Kev kho dua tshiab ntawm cov neeg tau txais kev pabcuam raug soj ntsuam los ntawm kev ntws cytometry8 wk tom qab hloov pauv.

Rau lymphopenia-induced homeostaticproliferation thwmsim, sib npaug ntawm cov purified splenicNK hlwb los ntawm CD45.1 los yog Ythdf2ΔNK CD45.2 nas tau cotransferred rau hauv Rag2−/−Il2rg−/- nas ua raws li kev soj ntsuam ntawm cov txheeb ze feem pua ​​ntawm pauv WT thiab Ythdf2 NKsplen NKcell. ntawm Rag2−/−Il2rg−/− cov neeg tau txais los ntawm kev ntws cytometry ntawm lub sijhawm qhia.

Rau cov metastatic melanomamodel, 106 IL-2– nthuav NK hlwb los ntawm Ythdf2ΔNK lossis Ythdf2WTmice tau txhaj iv rau hauv Rag2−/−Il2rg−/- nas. 1 d tom qab, B16F10cells (105) tau txhaj iv rau hauv nas. 14 d tom qab txhaj tshuaj, micewere euthanized rau postmortem tsom xam. Hauv qee qhov kev sim, cov cell tau sau nrog CTV (5 µM, Invitrogen) txhawm rau taug qab cellproliferation ua ntej hloov mus.

Hauv vivo trafficking assay

Rau kev kuaj NK cell lag luam los ntawm BM mus rau cov ntshav peripheral, 1 µg iv APC-labeled anti-CD45 antibody raug txhaj rau C57BL/6 nas. Ob feeb tom qab txhaj tshuaj tiv thaiv kab mob, themice tau euthanized tam sim ntawd, thiab cov BM hlwb tau sau rau cytometry ntws tom qab cov hlwb tau stained nrog CD3 thiab NK1.1 cov tshuaj tiv thaiv. Parenchymal NK hlwb raug txheeb xyuas los ntawm kev tsis muaj CD45 staining, thaum sinusoidal NK hlwb raug txheeb xyuas los ntawm qhov muaj CD45 labeling. Yog li, qhov piv ntawm NKcells hauv cov sinusoids (CD45+) rau qhov ntawd hauv thaj chaw parenchymal (CD45−) qhia tias NK cell lag luam los ntawm BM toperipheral cov ntshav nyob rau hauv lub xeev khov kho.

Real-time RT-qPCR thiab immunoblotting

RNA raug cais tawm siv RNeasy Mini Cov Khoom Siv (QIAGEN) thiab tom qab ntawd thim rov qab rau cDNA nrog PrimeScript RT Reagent Kitwith gDNA Eraser (Takara Bio) raws li cov chaw tsim khoom cov lus qhia. mRNA qhia theem tau txheeb xyuas siv SYBRGreen PCR Master Mix thiab QuantStudio 12K Flex Real-TimePCR System (ob leeg los ntawm Thermo Fisher Scientific). Primer sequences yog teev nyob rau hauv Table S1.

Immunoblotting tau ua raws li cov txheej txheem txheej txheem, raws li tau piav qhia yav dhau los (Denget al., 2015; Yu li al., 2006). Cov tshuaj tiv thaiv hauv qab no tau siv: METTL3 (cat. no. 15073-1-AP; Proteintech), METTL14 (cat. no.26158-1-AP; Proteintech), YTHDF1 (cat. no. 17479-1-AP ; Proteintech), YTHDF2 (cat. no. RN123PW; MBL), YTHDF3 (cat. no.25537-1-AP; Proteintech), ALKBH5 (cat. no. ab195377; Abcam), FTO (cat. no. ab124892; Abcam), MDM2 (cat. no. 33-7100; Invitrogen), TDP-43 (cat. no. PA5-29949; Invitrogen), thiab -actin(cat. no. {{20}) }}Ig; Proteintech).

siRNA knockdown assay

IL-2–expanded NK cells were transfected with Accell mouse Tardbp siRNA (cat. no. E-040078-00-0005; Dharmacon) or Mdm2 siRNA (cat. no. E-041098-00-0005; Dharmacon) using Accell delivery media (Dharmacon) according to the manufacturer's instructions in the presence of IL-15 (50 ng/ml). The Accell eGFP control pool was used as siRNA control. The transfection efficiency was >90% raws li ntsuas los ntawm flow cytometry. Geneknockdown efficiency tau txiav txim los ntawm qPCR thiab immunoblotting. 3 d tom qab transfection, cell apoptosis, thiab kev loj hlob tau soj ntsuam los ntawm kev ntws cytometry raws li tau piav qhia saum toj no.

Luciferase tus neeg sau xov xwm soj ntsuam

Ythdf2 txhawb nqa cheeb tsam xws li -2,000 bp rau +100 bpof lub TSS tau nthuav tawm los ntawm murine NK hlwb thiab cloned rau hauv apGL4-Basic Luciferase Reporter Vector (Promega) los tsim apGL{ {5}}Ythdf2 reporter plasmid. HEK293T hlwb yuav los ntawm ATCC tau cotransfected nrog pGL4-Ythdf2 reporter plasmidas zoo li STAT5a lossis STAT5b overexpression plasmids lossis anempty vector, ua ke nrog pRL-TK Renilla reporter plasmid (Promega) rau normalization ntawm transfection efficiency. Cov hlwb raug sau tseg rau lysis 24 teev tom qab hloov pauv, thiab luciferaseactivity tau suav nrog fluorimetrically nrog Dual-LuciferaseSystem (Promega). Primer sequences rau cloning Ythdf2promoter thiab STAT5a thiab STAT5b overexpression plasmids tau teev nyob rau hauv Table S1.

CHIP kev soj ntsuam

Chip kev soj ntsuam tau ua tiav siv Pierce Magnetic Chip Kit (cat. no. 26157; Thermo Fisher Scientific) raws li tus neeg tsim khoom cov lus qhia. Luv luv, qhov sib npaug ntawm ananti-anti-phospho-Stat5 (Tyr694, cat. No. 9351; Cell Signaling Technologies) los yog kev tswj hwm tus luav ib txwm IgG tau cais siv los ua kom muaj kev sib txuas ntawm DNA-protein complexes tau los ntawm 5 × 106 purified nas thawj NK hlwb uas tau pretreated nrog IL -15 (50 ng / ml) rau 1 h. Tom qab kev thim rov qab ntawm kev sib txuas, DNA immunoprecipitated los ntawm cov tshuaj tiv thaiv kab mob tau kuaj los ntawm qPCR. Cov kab ke ntawm allprimers tau teev nyob rau hauv Table S1.

Ex vivo cytotoxicity assay

Ex vivo cytotoxicity ntawm NK hlwb raug soj ntsuam los ntawm tus qauv 51Crrelease assays. Mouse lymphoma cell kab RMA-S (MHC class Ideficient) thiab RMA (MHC chav kawm kuv txaus) hlwb, khoom plig ntawm Andre'Veillette (McGill University, Montreal, Canada), tau siv cov hlwb astarget. Cov nas raug kho nrog ip txhaj tshuaj ntawm polyinosinic: polycytidylic acid [poly (I: C); 200 µg / nas] rau 18 h. Poly(I: C)-activated NK cells raug cais tawm ntawm tus po siv EasySepMouse NK Cell Isolation Kit (STEMCELL Technologies). PurifiedNK hlwb tau cocultured nrog lub hom phiaj ntawm qhov sib piv ntawm 5: 1, 2.5: 1, thiab 1.25: 1 nyob rau hauv muaj IL-2 (50 U / ml).

m6a qw

Purified splenic NK hlwb raug nthuav tawm los ntawm IL-2 (1, 000 U/ml, cat. no. Bulk Ro 23-6019; National Cancer Institute) in vitro for7 d. Tag Nrho RNA raug cais los ntawm TRIzol reagent (Thermo FisherScientific) los ntawm 50 lab IL-2- nthuav NK hlwb. Polyadenylated RNA tau ntxiv los ntawm tag nrho RNA los ntawm kev siv Dynabeads mRNA Purification Kit (Invitrogen). mRNA sampleswere fragmented into 100-nt-ntev fragments with RNA fragmentation reagents (Invitrogen).

Fragmented mRNA (5 µgmRNA) tau siv rau m6A immunoprecipitation siv ib qho m6Aantibody (202003; Synaptic) ua raws li tus qauv txheej txheem ntawm Magna MeRIP m6A Cov Khoom Siv (Merck Millipore). RNA tau txhawb nqa los ntawm RNA Clean & Concentrator-5 (Zymo Research) rau lub tsev qiv ntawv tsim nrog KAPA RNA HyperPrep Kit(Roche). Sequencing tau ua nyob rau hauv Lub Nroog Kev Cia Siab genomics qhov chaw ntawm lub tshuab Illumina HiSeq 2500 nrog tib nyeem 50-bp hom. Sequences nyeem tau mapped rau mousegenome siv HISAT2 v101 software (Kim li al., 2015).

Mappedreads ntawm immunoprecipitation thiab input cov tsev qiv ntawv tau muab siv R pob exomePeak (Meng li al., 2014). m6Apeaks tau pom zoo siv Integrative Genomics Viewersoftware (http://www.igv.org). Lub m6A-binding motif raug tshuaj xyuas los ntawm MEME (https://meme-suite.org) thiab HOMER (http://homer.ucsd.edu/homer/motif). Lub npe hu ua peaks tau piav qhia los ntawm kev sib tshuam nrog cov qauv tsim qauv siv Rpackage ChiPseeker (Yu li al., 2015).

StringTie was used to assess expression levels for mRNAs from input libraries by calculating the total exon fragments/mapped reads in millions × exon length in kb (Pertea et al., 2015). The differentially expressed mRNAs were selected with log2(fold change) >1 orlog2 (fold hloov)<−1 and P < 0.05 using the R package edgeR (Robinson et al., 2010).

YTHDF2 RIP-seq

50 lab IL-2– nthuav tawm NK hlwb raug sau thiab ntxuav ob zaug nrog txias PBS, thiab cov cell pellet tau lysed nrog 2 vol oflysis tsis (10 mM Hepes, pH 7.6, 150 mM KCl, 2 mM EDTA, 0.5% NP-40, 0.5 mM dithiothreitol, 1:100 protease inhibitorcocktail [Thermo Fisher Scientific], thiab 400 U/ml SUPERase-In RNase Inhibitor [Thermo Fisher]).

Lub lysate tau incubated rau dej khov rau 5 feeb thiab centrifuged rau 15 feeb kom tshem tau thelysate. Ib feem kaum ntawm cov xov tooj ntawm tes lysate tau txais kev cawmdim raws li cov tswv yim. Therest ntawm cov cell lysate tau incubated nrog 5 µg anti-YTHDF2 (cat.no. RN123PW; MBL) uas tau txuas nrog Protein A Sib Nqus Beads (cat. no. 10001D; Invitrogen) ntawm 4 degree rau 2 h withgentle tig. Tom qab ntawd, cov hlaws tau raug ntxuav tsib zaug nrog 1 ml dej khov-txias ntxhua khaub ncaws (50 mM HEPES, pH 7.6,200 mM NaCl, 2 mM EDTA, 0.05% NP-40, 0.5 mM dithiothreitol, thiab 200 U / ml RNase. inhibitor).

Cov qauv immunoprecipitated tau raug Proteinase K digestion hauv ntxuav buffersupplemented nrog 1% SDS thiab 2 mg / ml Proteinase K (ThermoFisher Scientific) incubated nrog co ntawm 1,200 rpm ntawm 55 degree rau 1 h. Tag Nrho RNA tau muab rho tawm los ntawm ob qho tib si tawm tswv yim thiab immunoprecipitated RNA los ntawm kev ntxiv 5 vol TRIzol reagent ua raws li Direct-zol RNA Miniprep (Zymo Research).

Lub tsev qiv ntawv cDNA tau tsim nrog KAPA RNA HyperPrep Cov Khoom Siv (Roche) thiab ua raws li ntawm Illumina HiSeq 2500 platform. Peak callingresults nrog immunoprecipitation thiab input cov tsev qiv ntawv tau tsim los ntawm R pob RIPSeeker (Li li al., 2013). HOMER tau siv los nrhiav motifs ntawm cov ntaub ntawv faib nyob rau hauv ncov cheeb tsam.Hu peaks tau annotated los ntawm kev sib tshuam nrog gene andtranscript architecture siv ChippeakAnno (Zhu li al., 2010).

mRNA kev soj ntsuam stability

Purified splenic NK hlwb los ntawm Ythdf2ΔNK thiab Ythdf2WT nas taucultured nrog IL-15 (50 ng/ml). 3 d tom qab kab lis kev cai, cov hlwb raug kho nrog actinomycin D (5 µg / ml, cat. no. A9415; Sigma) rau lub sijhawm qhia. Cells uas tsis muaj kev kho mob tau siv ntawm 0 h.Cells tau sau thaum lub sijhawm qhia, thiab tag nrho RNA raug rho tawm ntawm cov hlwb rau qPCR. Lub mRNA ib nrab-lub neej tau suav nrog cov txheej txheem yav dhau los tau piav qhia los ntawm Weng li al.(2018). Primer sequences yog teev nyob rau hauv Table S1.

Online database tsom xam

Peb siv cov peev txheej online BioGPS (http://biogps.org) los tshuaj xyuas cov ntaub so ntswg tshwj xeeb ntawm Ythdf2. Cov RNA-seqdata sets yog los ntawm GEO nyob rau hauv accession nos. GSE106138, GSE113214, thiab GSE25672. Cov ntaub ntawv zoo li qub los ntawm RNA-seq kev txheeb xyuas tau raug xa tawm, thiab cov noob qhia z-score tau pom nrog Heatmap.2 muaj nuj nqi hauv gplots Rlibrary

Kev txheeb cais

Unpaired Student's t-tests (ob-tailed) tau ua siv GraphPad Prism software. Ib-txoj kev lossis ob-txoj kev ANOVA tau ua tiav thaum peb lossis ntau pawg neeg ywj pheej raug muab piv. P qhov tseem ceeb tau hloov kho rau ntau qhov kev sib piv siv cov txheej txheem Holm-Sˇ´ıdak. P < 0.05 tau suav hais tias yog qhov tseem ceeb. *, P < {{10}}.05; **, P <0.01; thiab ***, P <0.001.

Online cov khoom siv ntxiv

Fig. S1 qhia txog qib protein ntau ntawm YTHDF2 hauv lub cev tiv thaiv kab mob, suav nrog NK hlwb hauv kev teb rau IL-15 stimulation, MCMV kab mob, thiab qog nqaij hlav; tiam ntawm nas nrog NKcell-tshwj xeeb tshem tawm ntawm Ythdf2. Fig. S2 qhia cov kab mob titers hauv tus po thiab lub siab los ntawm cov nas uas kis MCMV thiab feem pua ​​thiab tus naj npawb ntawm Ly49H+ thiab/lossis Ly49D+ NKcells hauv cov nas kis MCMV. Fig. S3 qhia txog kev loj hlob, kev ciaj sia, kev loj hlob, thiab kev nthuav qhia ntawm kev ua kom thiab inhibitory receptors ntawm NK hlwb los ntawm Ythdf2WT thiab Ythdf2ΔNK nas. Fig.S4 qhia txog kev cai ntawm YTHDF2 qhia los ntawm IL-15-STAT5signaling thiab kev qhia ntawm cov khoom ntawm IL-15 receptors, PI3K-AKT txoj hauv kev, thiab MEK-ERK txoj hauv kev hauvNK hlwb los ntawm Ythdf2WT thiab Ythdf2ΔNK nas. Fig. S5 showtranscriptome-wide RNA-seq, m6A-seq, and RIP-seq assays inNK cells. Table S1 teev cov primers siv nyob rau hauv txoj kev tshawb no.

Cov ntaub ntawv muaj

Cov ntaub ntawv RNA-seq, m6A-seq, thiab RIP-seq tau muab tso rau hauv National Center for Biotechnology Information GEO nyob rau hauv accession no. TSO 174027. Cov ntaub ntawv tseem ceeb uas txhawb nqa qhov kev tshawb pom ntawm qhov kev tshawb fawb no muaj los ntawm cov kws sau ntawv sib xws thaum thov.

Kev lees paub

Txoj haujlwm no tau txais kev txhawb nqa los ntawm National Institutes of Health (NS106170, AI129582, CA247550, CA163205, CA223400, CA068458, thiab CA210087), Leukemia thiab Lymphoma Society (1364-19), Lub Tsev Kho Mob Cuam Tshuam California rau ReDI (1364-19) 9}}), thiab Lub Koom Haum Mob Cancer Alliance 2021 Exceptional ProjectAward. Txoj haujlwm no kuj tau txais kev txhawb nqa ib nrab los ntawm USDAaward (USDA/NIFA 2020-67017-30843).

Cov kws sau ntawv cov nyiaj pab: S. Ma, J. Yu, thiab MA Caligiuriconceived thiab tsim qhov project. Ma, J. Yan, J. Zhang, J. Yu ua qhov kev sim thiab/lossis cov ntaub ntawv txheeb xyuas. Z. Chen, L.-S.Wang, JC Sun, thiab J. Chen tau pab txhawb cov khoom siv thiab cov khoom siv. S. Ma, J. Yu, J. Chen, thiab MA Caligiuri tau sau, tshuaj xyuas, thiab/lossis kho daim ntawv. Txhua tus kws sau ntawv tau sib tham txog cov txiaj ntsig thiab tawm tswv yim ntawm cov ntawv sau.

Tshaj tawm: J. Chen qhia "lwm yam" los ntawm Genovel BiotechCorp. sab nraum cov ntaub ntawv xa mus thiab yog tus tsim kev tshawb fawb ntawm Genovel Biotech Corp. thiab tus kws pab tswv yim tshawb fawb ntawm haiv neeg oncology.Tsis muaj lwm yam kev tshaj tawm.

Cov ntaub ntawv

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