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Series GSE237359 Query DataSets for GSE237359
Status Public on Aug 31, 2023
Title A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Third-party reanalysis
Summary During human lung development the distal tip epithelial cells act as multipotent progenitors. From ~15 pcw (post conception weeks) the human tip epithelium retains progenitor marker expression, but also upregulates markers of the AT2 lineage. Immature AT2 cells appear in the tissue from 17 pcw. We have recently shown that 16-22 pcw epithelial tip cells can be expanded as organoids and differentiated to AT2 cells. However, the differentiated AT2 cells were not proliferative, limiting their use for functional studies and genetic manipulation. We have now developed a highly robust, efficient, and scalable culture condition (AT2 medium) that induces the differentiation of 16-22 pcw fetal lung tip cells into mature AT2 cells which grow as expandable 3D organoids. In this study, we characterise the fetal-derived AT2 cells, showing that they are stable over long-term passaging, efficiently process and secrete surfactant, and can differentiate into AT1 cells in vitro and in mouse lung transplantation assays. Forward genetic screen identifies candidate effectors of SFTPC trafficking which we validate using CRISPR interference (CRISPRi) in the AT2 organoids. We show that the trafficking of SFTPC requires ubiquitination by HECT domain E3 ligases, particularly Itch, and that their depletion phenocopies the pathological redistribution seen for the SFTPCI73T variant.
 
Overall design Four biological AT2 organoid lines cultured in AT2 medium were used for RNA seq analysis; each at early and late passages.
Four biological AT2 organoid lines cultured in AT2 medium were used for single cell RNA seq.

>> AT2_merged.gene_counts_length_scaled.tsv <<
A comparison between the RNA sequencing data of AT2 organoids and publicly available data of fetal organoid types and other alveolar cell types was performed:

fetal early tip progenitor organoids GSM5393370 and GSM5393371; fetal late tip progenitor organoids6 GSM5393372 and GSM5393373; PSC-iAT2s7 GSM5578511, GSM5578512 and GSM5578513; cultured adult AT2 cells7 GSM5578508, GSM5578509 and GSM5578510; freshly isolated adult AT2 cells8 GSM2537127, GSM2537128 and GSM2537129

Re-analysed Samples in GSE184143/PRJNA763363, GSE96642/PRJNA379280, GSE178528/PRJNA739556:

data column header; re-analyzed sample accns and title
adult_AT2_1; GSM2537127 SRR5345478 SAMN06603895 Adult AEC2_A
adult_AT2_2; GSM2537128 SRR5345479 SAMN06603915 Adult AEC2_B
adult_AT2_3; GSM2537129 SRR5345480 SAMN06603914 Adult AEC2_C
adult_AT2_CKDCI_1; GSM5578508 SRR15902408 SAMN21438592 adult_AT2_CKDCI_MRC5_1
adult_AT2_CKDCI_2; GSM5578509 SRR15902409 SAMN21438593 adult_AT2_CKDCI_MRC5_2
adult_AT2_CKDCI_3; GSM5578510 SRR15902410 SAMN21438594 adult_AT2_CKDCI_MRC5_3
Early_tip_progenitor_1; GSM5393372 SRR14869977 SAMN19792069 14404_folded_P2_RNA-seq
Early_tip_progenitor_2; GSM5393373 SRR14869978 SAMN19792068 14387_folded_P3_RNA-seq
Late_tip_progenitor_1; GSM5393370 SRR14869975 SAMN19792071 BRC1915_CS20_P5_RNA-seq
Late_tip_progenitor_2; GSM5393371 SRR14869976 SAMN19792070 13393_CS23_P5_RNA-seq
PSC_iAT2_3D_CKDCI_1; GSM5578511 SRR15902411 SAMN21438595 iAT2_3D_CKDCI_1
PSC_iAT2_3D_CKDCI_2; GSM5578512 SRR15902412 SAMN21438596 iAT2_3D_CKDCI_2
PSC_iAT2_3D_CKDCI_3; GSM5578513 SRR15902413 SAMN21438597 iAT2_3D_CKDCI_3
Web link https://github.com/brianpenghe/2024_AT2_organoids
 
Contributor(s) He P, Delpiano L, Lim K, Rawlins EL
Citation(s) 37693487
Submission date Jul 14, 2023
Last update date Apr 29, 2024
Contact name Kyungtae Lim
E-mail(s) kl492@cam.ac.uk, ktlim492@korea.ac.kr
Organization name University of Cambridge
Department Gurdon Institute
Lab Emma Rawlins
Street address Tennis Court Road
City Cambridge
ZIP/Postal code CB2 1QN
Country United Kingdom
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (9)
GSM7610401 AT2_1_E
GSM7610402 AT2_1_L
GSM7610403 AT2_2_E
Relations
BioProject PRJNA994820

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
GSE237359_AT2_merged.gene_counts_length_scaled.tsv.gz 3.2 Mb (ftp)(http) TSV
GSE237359_RAW.tar 811.0 Mb (http)(custom) TAR (of BIGWIG, H5AD)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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