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Series GSE151796 Query DataSets for GSE151796
Status Public on Jun 05, 2020
Title Comparison of two human organoid models of lung and intestinal inflammation reveals Toll-like receptor signalling activation and monocyte recruitment.
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary OBJECTIVES: The activation of immune responses in mucosal tissues is a key factor for the development and sustainment of several pathologies including infectious diseases and autoimmune diseases. However, translational research and personalized medicine struggle to advance because of the lack of suitable preclinical models that successfully mimic the complexity of human tissues without relying on in vivo mouse models. Here we propose two in vitro human 3D tissue models, deprived of any resident leukocytes, to model mucosal tissue inflammatory processes.
METHODS: We developed human 3D lung and intestinal organoids differentiated from induced pluripotent stem cells to model mucosal tissues. We then compared their response to a panel of microbial ligands and investigated their ability to attract and host human primary monocytes.
RESULTS: Mature lung and intestinal organoids incorporated epithelial (EpCAM+) and mesenchymal (CD73+) cells which responded to toll-like receptor stimulation by releasing pro-inflammatory cytokines and expressing tissue inflammatory markers including MMP9, COX2 and CRP. When added to the organoid culture, primary human monocytes migrated towards the organoids and began to differentiate to an “intermediate-like” phenotype characterised by increased levels of CD14 and CD16.
CONCLUSION: We show that human mucosal organoids exhibit proper immune functions and successfully mimic an immunocompetent tissue micro-environment able to host patient-derived immune cells. Our experimental setup provides a novel tool to tackle the complexity of immune responses in mucosal tissues which can be tailored to different human pathologies.
 
Overall design mRNA transcriptome of human lung and intestinal organoids treated with LPS or Poly(I:C)
 
Contributor(s) Jose SS, De Zuani M, Tidu F, Kohoutkova MH, Pazzagli L, Forte G, Spaccapelo R, Zelante T, Fric J
Citation(s) 32377340
Submission date Jun 04, 2020
Last update date Jun 07, 2020
Contact name Marco De Zuani
Organization name FNUSA - ICRC
Department CTM
Lab CMI
Street address Pekarska, 53
City Brno
ZIP/Postal code 65691
Country Czech Republic
 
Platforms (1)
GPL21697 NextSeq 550 (Homo sapiens)
Samples (24)
GSM4591025 Intestinal organoid - untreated_rep1 [IO-NT-1]
GSM4591026 Intestinal organoid - untreated_rep2 [IO-NT-2]
GSM4591027 Intestinal organoid - untreated_rep3 [IO-NT-3]
Relations
BioProject PRJNA637292
SRA SRP265949

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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
GSE151796_ALL_FeatureCounts.csv.gz 1.3 Mb (ftp)(http) CSV
GSE151796_RAW.tar 105.3 Mb (http)(custom) TAR (of TSV)
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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