← All datasets

GSE153264

GSE GEO
View on GEO Export SRA CSV

Definition of a Small Core Transcriptional Circuit Regulated by AML1-ETO [RNA-seq]

Organism: Homo sapiens
Platform: GPL18573
Samples: 16
Experiment Types:
Expression profiling by high throughput sequencing
Submitted: Jun 25 2020
Last Updated: Apr 01 2021
Status: Public on Dec 31 2020
Contact: Scott,,Hiebert (Vanderbilt University)

Relations

SubSeries of: GSE153281 BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA641888 SRA: https://www.ncbi.nlm.nih.gov/sra?term=SRP268835

Summary

Transcription factors regulate gene networks controlling normal hematopoiesis and are frequently deregulated in acute myeloid leukemia (AML). Critical to our understanding of the mechanism of cellular transformation by oncogenic transcription factors is the ability to define their direct gene targets. However, gene network cascades can change within minutes to hours, making it difficult to distinguish direct from secondary or compensatory transcriptional changes by traditional methodologies. Utilizing CRISPR-based genome editing, we inserted a degron tag into the endogenous AML1-ETO locus of Kasumi-1 cells, as well as overexpressed a degradable AML1-ETO protein in CD34+ human cord blood cells. This allowed rapid AML1-ETO protein degradation upon addition of a proteolysis targeting chimera (PROTAC). Furthermore, by combining rapid degradation with nascent transcript analysis (PRO-seq), RNA-seq and Cut&Run, we have defined the core AML1-ETO regulatory network. De-repression of this small set of genes set off a cascade of transcriptional events resulting in myeloid differentiation.

Overall Design

RNA-seq was performed using biological replicates. For Kasumi-1 cell samples, parental cells as well as untreated AML1-ETO-FKB12F36V cells served as negative controls. Cells were harvested at 2, 4, 8, and 24 hr post-treatment with dTAG-47 to induce AML1-ETO-FKBP12F36V degradation. For CD34+ human cord blood cultures expressing AML1-ETO-FKBP12F36V, RNA-seq was performed on biological replicates treated with dTAG-47 for 4 hours and compared with DMSO-treated control samples.

Analysis (3 steps)

View Data Processing
Processing steps for GSE153264
  1. Adaptors were trimmed using trimmomatic (SE for Kasumi-1 cells, PE for CD34+ cells).
  2. Trimmed reads were aligned to the human genome (hg19) with TopHat v2.0.11.
  3. Differential gene expression was determined using Cuffdiff v.2.1.1.

Supplementary Files (6)

GSE153264_0hr_v_24hr_gene_exp.diff.gz Download
GSE153264_0hr_v_2hr_gene_exp.diff.gz Download
GSE153264_0hr_v_4hr_gene_exp.diff.gz Download
GSE153264_0hr_v_8hr_gene_exp.diff.gz Download
GSE153264_CD34_DMSO_v_dTAG-4hr_gene_exp.diff.gz Download
GSE153264_parental_v_0hr_gene_exp.diff.gz Download
GEO Samples (16)
GSM4637185 GSM4637186 GSM4637187 GSM4637188 GSM4637189 GSM4637190 GSM4637191 GSM4637192 GSM4637193 GSM4637194 GSM4637195 GSM4637196 GSM4637197 GSM4637198 GSM4637199 GSM4637200

Dataset Citations (1)

PubMed citation (PMID 33382982)

SRA Experiments (16) and Runs (16)

Total: 21285 MB
SRX8617696 SRP268835 RNA-Seq SINGLE
GSM4637185: Kasumi-1_parental-1 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906740
BioProject: PRJNA641888
BioSample: SAMN15369529
Platform: ILLUMINA
Instrument: NextSeq 500
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1 cells
cell line: Kasumi-1
genotype/variation: Parental
treatment: Untreated
Original files (1)
Kasumi-1 cells
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091803 33395385 2504653875 856.18 2023-KS-1-ATTACTCG-TAAGATTA_S1_R1_001.fastq.gz, SRR12091803, SRR12091… SRA
SRX8617697 SRP268835 RNA-Seq SINGLE
GSM4637186: Kasumi-1_parental-2 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906741
BioProject: PRJNA641888
BioSample: SAMN15369527
Platform: ILLUMINA
Instrument: NextSeq 500
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1 cells
cell line: Kasumi-1
genotype/variation: Parental
treatment: Untreated
Original files (1)
Kasumi-1 cells
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091804 31345412 2350905900 803.11 2023-KS-2-TCCGGAGA-TAAGATTA_S2_R1_001.fastq.gz, SRR12091804, SRR12091… SRA
SRX8617698 SRP268835 RNA-Seq SINGLE
GSM4637187: Kasumi-1_AE-FKBP_dTAG_0hr-1 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906742
BioProject: PRJNA641888
BioSample: SAMN15369524
Platform: ILLUMINA
Instrument: NextSeq 500
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1 cells
cell line: Kasumi-1
genotype/variation: AML1-ETO-FKBP12F36V
treatment: Untreated
time point: 0hr
Original files (1)
Kasumi-1 cells
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091805 31325221 2349391575 804.67 2023-KS-3-CGCTCATT-TAAGATTA_S3_R1_001.fastq.gz, SRR12091805, SRR12091… SRA
SRX8617699 SRP268835 RNA-Seq SINGLE
GSM4637188: Kasumi-1_AE-FKBP_dTAG_0hr-2 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906743
BioProject: PRJNA641888
BioSample: SAMN15369522
Platform: ILLUMINA
Instrument: NextSeq 500
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1 cells
cell line: Kasumi-1
genotype/variation: AML1-ETO-FKBP12F36V
treatment: Untreated
time point: 0hr
Original files (1)
Kasumi-1 cells
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091806 33369470 2502710250 856.77 2023-KS-4-GAGATTCC-TAAGATTA_S4_R1_001.fastq.gz, SRR12091806, SRR12091… SRA
SRX8617700 SRP268835 RNA-Seq SINGLE
GSM4637189: Kasumi-1_AE-FKBP_dTAG_2hr-1 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906744
BioProject: PRJNA641888
BioSample: SAMN15369520
Platform: ILLUMINA
Instrument: NextSeq 500
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1 cells
cell line: Kasumi-1
genotype/variation: AML1-ETO-FKBP12F36V
treatment: 500 nM dTAG-47
time point: 2hr
Original files (1)
Kasumi-1 cells
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091807 34318854 2573914050 878.01 2023-KS-5-ATTCAGAA-TAAGATTA_S5_R1_001.fastq.gz, SRR12091807, SRR12091… SRA
SRX8617701 SRP268835 RNA-Seq SINGLE
GSM4637190: Kasumi-1_AE-FKBP_dTAG_2hr-2 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906745
BioProject: PRJNA641888
BioSample: SAMN15369519
Platform: ILLUMINA
Instrument: NextSeq 500
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1 cells
cell line: Kasumi-1
genotype/variation: AML1-ETO-FKBP12F36V
treatment: 500 nM dTAG-47
time point: 2hr
Original files (1)
Kasumi-1 cells
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091808 30456323 2284224225 778.96 2023-KS-6-GAATTCGT-TAAGATTA_S6_R1_001.fastq.gz, SRR12091808, SRR12091… SRA
SRX8617702 SRP268835 RNA-Seq SINGLE
GSM4637191: Kasumi-1_AE-FKBP_dTAG_4hr-1 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906746
BioProject: PRJNA641888
BioSample: SAMN15369517
Platform: ILLUMINA
Instrument: NextSeq 500
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1 cells
cell line: Kasumi-1
genotype/variation: AML1-ETO-FKBP12F36V
treatment: 500 nM dTAG-47
time point: 4hr
Original files (1)
Kasumi-1 cells
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091809 30161113 2262083475 772.45 2023-KS-7-CTGAAGCT-TAAGATTA_S7_R1_001.fastq.gz, SRR12091809, SRR12091… SRA
SRX8617703 SRP268835 RNA-Seq SINGLE
GSM4637192: Kasumi-1_AE-FKBP_dTAG_4hr-2 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906747
BioProject: PRJNA641888
BioSample: SAMN15369515
Platform: ILLUMINA
Instrument: NextSeq 500
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1 cells
cell line: Kasumi-1
genotype/variation: AML1-ETO-FKBP12F36V
treatment: 500 nM dTAG-47
time point: 4hr
Original files (1)
Kasumi-1 cells
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091810 27060905 2029567875 697.74 2023-KS-8-TAATGCGC-TAAGATTA_S8_R1_001.fastq.gz, SRR12091810, SRR12091… SRA
SRX8617704 SRP268835 RNA-Seq SINGLE
GSM4637193: Kasumi-1_AE-FKBP_dTAG_8hr-1 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906748
BioProject: PRJNA641888
BioSample: SAMN15369513
Platform: ILLUMINA
Instrument: NextSeq 500
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1 cells
cell line: Kasumi-1
genotype/variation: AML1-ETO-FKBP12F36V
treatment: 500 nM dTAG-47
time point: 8hr
Original files (1)
Kasumi-1 cells
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091811 28478891 2135916825 734.05 2023-KS-9-CGGCTATG-TAAGATTA_S9_R1_001.fastq.gz, SRR12091811, SRR12091… SRA
SRX8617705 SRP268835 RNA-Seq SINGLE
GSM4637194: Kasumi-1_AE-FKBP_dTAG_8hr-2 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906749
BioProject: PRJNA641888
BioSample: SAMN15369512
Platform: ILLUMINA
Instrument: NextSeq 500
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1 cells
cell line: Kasumi-1
genotype/variation: AML1-ETO-FKBP12F36V
treatment: 500 nM dTAG-47
time point: 8hr
Original files (1)
Kasumi-1 cells
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091812 36216719 2716253925 933.43 2023-KS-10-TCCGCGAA-TAAGATTA_S10_R1_001.fastq.gz, SRR12091812, SRR120… SRA
SRX8617706 SRP268835 RNA-Seq SINGLE
GSM4637195: Kasumi-1_AE-FKBP_dTAG_24hr-1 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906750
BioProject: PRJNA641888
BioSample: SAMN15369511
Platform: ILLUMINA
Instrument: NextSeq 500
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1 cells
cell line: Kasumi-1
genotype/variation: AML1-ETO-FKBP12F36V
treatment: 500 nM dTAG-47
time point: 24hr
Original files (1)
Kasumi-1 cells
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091813 37954171 2846562825 983.75 2023-KS-11-TCTCGCGC-TAAGATTA_S11_R1_001.fastq.gz, SRR12091813, SRR120… SRA
SRX8617707 SRP268835 RNA-Seq SINGLE
GSM4637196: Kasumi-1_AE-FKBP_dTAG_24hr-2 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906751
BioProject: PRJNA641888
BioSample: SAMN15369510
Platform: ILLUMINA
Instrument: NextSeq 500
Organism: Homo sapiens
Sample attributes
source_name: Kasumi-1 cells
cell line: Kasumi-1
genotype/variation: AML1-ETO-FKBP12F36V
treatment: 500 nM dTAG-47
time point: 24hr
Original files (1)
Kasumi-1 cells
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091814 31322550 2349191250 798.03 2023-KS-12-AGCGATAG-TAAGATTA_S12_R1_001.fastq.gz, SRR12091814, SRR120… SRA
SRX8617708 SRP268835 RNA-Seq PAIRED
GSM4637197: CD34_AML1-ETO-FKBP-DMSO_4hr-1 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906752
BioProject: PRJNA641888
BioSample: SAMN15369509
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: CD34+ human cord blood
cell type: CD34+ cord blood cells
genotype/variation: AML1-ETO-FKBP12F36V
treatment: DMSO
time point: 4hr
Original files (1)
CD34+ human cord blood
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091815 29173611 8752083300 2742.57 4582-KS-1_S9_L005_R1_001.fastq.gz, 4582-KS-1_S9_L005_R2_001.fastq.gz,… SRA
SRX8617709 SRP268835 RNA-Seq PAIRED
GSM4637198: CD34_AML1-ETO-FKBP-DMSO_4hr-2 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906753
BioProject: PRJNA641888
BioSample: SAMN15369508
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: CD34+ human cord blood
cell type: CD34+ cord blood cells
genotype/variation: AML1-ETO-FKBP12F36V
treatment: DMSO
time point: 4hr
Original files (1)
CD34+ human cord blood
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091816 31285251 9385575300 2971.75 4582-KS-2_S10_L005_R1_001.fastq.gz, 4582-KS-2_S10_L005_R2_001.fastq.g… SRA
SRX8617710 SRP268835 RNA-Seq PAIRED
GSM4637199: CD34_AML1-ETO-FKBP-dTAG_4hr-1 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906754
BioProject: PRJNA641888
BioSample: SAMN15369507
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: CD34+ human cord blood
cell type: CD34+ cord blood cells
genotype/variation: AML1-ETO-FKBP12F36V
treatment: 500 nM dTAG-47
time point: 4hr
Original files (1)
CD34+ human cord blood
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091817 32385053 9715515900 3052.48 4582-KS-3_S11_L005_R1_001.fastq.gz, 4582-KS-3_S11_L005_R2_001.fastq.g… SRA
SRX8617711 SRP268835 RNA-Seq PAIRED
GSM4637200: CD34_AML1-ETO-FKBP-dTAG_4hr-2 [RNA-seq]; Homo sapiens; RNA-Seq
Sample: SRS6906755
BioProject: PRJNA641888
BioSample: SAMN15369506
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Homo sapiens
Sample attributes
source_name: CD34+ human cord blood
cell type: CD34+ cord blood cells
genotype/variation: AML1-ETO-FKBP12F36V
treatment: 500 nM dTAG-47
time point: 4hr
Original files (1)
CD34+ human cord blood
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR12091818 27771448 8331434400 2621.3 4582-KS-4_S12_L005_R1_001.fastq.gz, 4582-KS-4_S12_L005_R2_001.fastq.g… SRA

Linked Publications (1)

Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML.
Cell reports · 2022

Data Files (16)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
— 2023-KS-10-TCCGCGAA-TAAGATTA_S10_R1_001.fastq.gz RNA-Seq 933.4 MB link
— 2023-KS-11-TCTCGCGC-TAAGATTA_S11_R1_001.fastq.gz RNA-Seq 983.8 MB link
— 2023-KS-12-AGCGATAG-TAAGATTA_S12_R1_001.fastq.gz RNA-Seq 798.0 MB link
— 2023-KS-1-ATTACTCG-TAAGATTA_S1_R1_001.fastq.gz RNA-Seq 856.2 MB link
— 2023-KS-2-TCCGGAGA-TAAGATTA_S2_R1_001.fastq.gz RNA-Seq 803.1 MB link
— 2023-KS-3-CGCTCATT-TAAGATTA_S3_R1_001.fastq.gz RNA-Seq 804.7 MB link
— 2023-KS-4-GAGATTCC-TAAGATTA_S4_R1_001.fastq.gz RNA-Seq 856.8 MB link
— 2023-KS-5-ATTCAGAA-TAAGATTA_S5_R1_001.fastq.gz RNA-Seq 878.0 MB link
— 2023-KS-6-GAATTCGT-TAAGATTA_S6_R1_001.fastq.gz RNA-Seq 779.0 MB link
— 2023-KS-7-CTGAAGCT-TAAGATTA_S7_R1_001.fastq.gz RNA-Seq 772.4 MB link
— 2023-KS-8-TAATGCGC-TAAGATTA_S8_R1_001.fastq.gz RNA-Seq 697.7 MB link
— 2023-KS-9-CGGCTATG-TAAGATTA_S9_R1_001.fastq.gz RNA-Seq 734.0 MB link
— 4582-KS-1_S9_L005_R1_001.fastq.gz RNA-Seq 2.7 GB link
— 4582-KS-2_S10_L005_R1_001.fastq.gz RNA-Seq 2.9 GB link
— 4582-KS-3_S11_L005_R1_001.fastq.gz RNA-Seq 3.0 GB link
— 4582-KS-4_S12_L005_R1_001.fastq.gz RNA-Seq 2.6 GB link