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Series GSE136929 Query DataSets for GSE136929
Status Public on Sep 05, 2020
Title Human embryonic stem cell-derived organoidal retinoblastoma reveals cancerous origin and therapeutic target
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Retinoblastoma (Rb) is the most prevalent intraocular malignant tumor in children with less than 30% survival rate globally. Rb genetic predisposition has been well defined for decades, whereas its developmental origin and drug agents remain largely unexplored. Here we developed the first organoidal retinoblastoma model derived from human embryonic stem cells (hESCs) with a biallelic knockout (RB1-/-) or mutagenesis (RB1Mut/Mut) of the RB1 gene, which exhibit extreme consistent properties of Rb tumorigenesis, transcriptome, and genome-wide methylation. Using single-cell RNA-seq and immunostaining of this model, we found that developmentally Rb originated from ARR3+ maturing cone precursors and a new cell type of unfolded protein response occurred in the organoidal retinoblastoma. A key PI3K-Akt pathway was aberrantly regulated, and its strong activator SYK (encoding proto-oncogenic spleen tyrosine kinase) was significantly upregulated in the cancerous organoids. Furthermore, we demonstrated that the SYK inhibitors, A502 and B502, have more significant therapeutic response on the early-stage organoidal retinoblastoma compared to four well-established chemotherapeutic drugs in clinic. Collectively, we established a brand-new organoidal retinoblastoma model derived from human ESCs in-a-dish and discovered its cell-of-origin and potential drug agents, shedding light on development and therapeutics of human cancers.
Overall design Whole-Genome Bisulfite Sequencing of 120-day old human Rb organoids (hRBOs) and normal human retinal organoids (hROs).
Transcription profiles of human Rb organoids (hRBOs) and normal human retinal organoids (hROs) at different organoid stages were characterized using RNA-Seq sequencing (RNA-seq).
Transcription profiles of human Rb organoids (hRBOs) and normal human retinal organoids (hROs) at day 90 were characterized using single-cell RNA-Seq sequencing (scRNA-seq).
Contributor(s) Liu H, Zhang Y, Zhang Y, Li Y, Hua Z, Han F, Jin S, Zhang C, Wu K, Lv J, Yu F, Lin Q, Chen C, Su J, Jin Z
Citation(s) 33318192
Submission date Sep 05, 2019
Last update date Jul 25, 2021
Contact name Zibing Jin
Organization name Laboratory for Stem Cell & Retinal Regeneration, Institute of Stem Cell Research
Department Division of Ophthalmic Genetics, The Eye Hospital
Lab Jin lab
Street address No.270, Xueyuan road
City Wenzhou
State/province Zhejiang
ZIP/Postal code 325000
Country China
Platforms (3)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL20795 HiSeq X Ten (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (89)
GSM4061950 hRBO-D120
GSM4061951 hRO-D120
GSM5468100 D0 WT hESC rep1 RNA-seq
BioProject PRJNA564075
SRA SRP220467

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

Supplementary file Size Download File type/resource
GSE136929_RAW.tar 635.0 Mb (http)(custom) TAR (of BW, CSV, MTX, TSV)
GSE136929_ref_trans_full_table.Day0.txt.gz 1.4 Mb (ftp)(http) TXT
GSE136929_ref_trans_full_table.Day105-120.txt.gz 3.1 Mb (ftp)(http) TXT
GSE136929_ref_trans_full_table.Day30-45.txt.gz 1.8 Mb (ftp)(http) TXT
GSE136929_ref_trans_full_table.Day60-75-90.txt.gz 4.9 Mb (ftp)(http) TXT
GSE136929_ref_trans_full_table.Y79.txt.gz 775.5 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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