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Series GSE134388 Query DataSets for GSE134388
Status Public on Aug 10, 2020
Title ALKBH5 regulates anti-PD-1 therapy response by modulating lactate and suppressive immune cell accumulation in tumor microenvironment
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary We performed RNA-Seq and m6A RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-Seq) to determine whether the altered gene expression and the regulatory functions in cancer immunotherapy could be a consequence of Alkbh5 or Fto-mediated m6A/m6Am demethylation. We used two m6A peak calling algorithms to find the common peaks between the two methods, and only kept the conserved peaks detected in all the biological replicates of each group to obtain the most stringent results. Our data suggest that the enzymatic activity and the altered m6A/m6Am peaks of Fto and Alkbh5 knockout had similarity but also had obvious distinct features, which may lead to the different mechanisms of the two protein to exert their functions in regulating immunotherapy. In addition, we performed single cell RNA-seq on a tumor obtained from a patient who had stage IV melanoma progressive disease and responded well to PD-1 blockage therapy. We observed substantial immune cell infiltration and very few residual melanoma cells, indicators of good immunotherapy responses. We then examined ALKBH5 expression and found that there were more melanoma cells expressing ALKBH5 than the surrounding normal control cells.
 
Overall design NTC control, Alkbh5 KO, Fto KO mouse tumors after cancer immunotherapy were analyzed by RNA-Seq and MeRIP-Seq. Tumors from a melanoma patient who had stage IV melanoma progressive disease and responded well to PD-1 blockage therapy were analyzed by single cell RNA-seq.
 
Contributor(s) Li N, Kang Y, Rana T
Citation(s) 32747553
Submission date Jul 17, 2019
Last update date Sep 08, 2020
Contact name Na Li
E-mail(s) nal023@health.ucsd.edu
Organization name University of California, San Diego
Department Pediatrics
Lab Tariq Rana's Lab
Street address 9500 Gilman Dr
City La Jolla
State/province California
ZIP/Postal code 92037
Country USA
 
Platforms (2)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (21)
GSM3945593 B16F10-Alkbh5 knockout cells implanted tumor-Mouse 1 [Input_MeRIP-Seq]
GSM3945594 B16F10-Alkbh5 knockout cells implanted tumor-Mouse 2 [Input_MeRIP-Seq]
GSM3945595 B16F10-Fto knockout cells implanted tumor-Mouse 1 [Input_MeRIP-Seq]
Relations
BioProject PRJNA555097
SRA SRP215207

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE134388_ALK.bb 228.8 Kb (ftp)(http) BB
GSE134388_DEseq2_count.xlsx 1.8 Mb (ftp)(http) XLSX
GSE134388_FTO.bb 113.4 Kb (ftp)(http) BB
GSE134388_NTC.bb 237.6 Kb (ftp)(http) BB
GSE134388_RAW.tar 25.9 Mb (http)(custom) TAR (of MTX, TSV, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file
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