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| Status |
Public on Jan 11, 2019 |
| Title |
Whole transcriptome analysis reveals a pro-inflammatory profile of ductular reaction cells in AH. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Objective: Alcoholic hepatitis (AH) is characterized by the expansion of ductular reaction (DR) cells and expression of liver progenitor cell (LPC) markers. The aim of this study was to identify the gene expression profile and associated genes of DR cells and to evaluate its weight in alcoholic disease progression. Design: KRT7+, KRT7- and total liver fractions were laser microdissected from liver biopsies (n=6) of patients with AH and whole transcriptome was sequenced. Gene signature was assessed in transcriptomic data from 41 patients with alcoholic liver disease. Pro-inflammatory profile was evaluated in tissue and serum samples and in human LPC organoids. Results: Transcriptome analysis of KRT7+ DR cells uncovered intrinsic gene pathways of DR and allowed identifying genes associated with DR expressed in AH. In addition, DR gene signature and associated genes correlated with disease progression and poor outcome in AH patients. Importantly, DR presented a pro-inflammatory profile with expression of CXC and CCL chemokines and was associated with infiltrating neutrophils. Moreover, LPC markers correlated with liver expression and circulating levels of inflammatory mediators. In vitro, human LPC organoids mimicked ductular reaction gene expression profile and produced chemokines. Moreover, LPC promoted neutrophil migration and enhanced their inflammatory profile. Conclusions: Here we report for the first time the gene expression signature of DR in AH and its association with disease progression. Functional and experimental analysis demonstrates that DR cells have a pro-inflammatory profile, and suggest their involvement in neutrophil recruitment and liver inflammatory response.
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| Overall design |
The genome wide transcriptome of 4 Liver organoids and 4 compensated cirrhotic liver samples were assessed using Affymetrix HG-U219 genechips (Affymetrix)
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| Contributor(s) |
Coll M, Aguilar B, Lozano JJ, Sancho P |
| Citation(s) |
30565271 |
| Submission date |
Jul 07, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Juanjo Lozano |
| E-mail(s) |
juanjo.lozano@ciberehd.org
|
| Organization name |
CIBEREHD
|
| Department |
Plataforma de Bioinformatica
|
| Street address |
C/ Rosselló 153
|
| City |
Barcelona |
| ZIP/Postal code |
08036 |
| Country |
Spain |
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|
| Platforms (1) |
| GPL13667 |
[HG-U219] Affymetrix Human Genome U219 Array |
|
| Samples (8)
|
| GSM2695864 |
Liver progenitor cell organoids transcriptome 521 |
| GSM2695865 |
Liver progenitor cell organoids transcriptome 995 |
| GSM2695866 |
Liver progenitor cell organoids transcriptome HB6 |
| GSM2695867 |
Liver progenitor cell organoids transcriptome HB9 |
| GSM2695868 |
compensated cirrhotic liver tissue transcriptome LM 29 |
| GSM2695869 |
compensated cirrhotic liver tissue transcriptome LM 30 |
| GSM2695870 |
compensated cirrhotic liver tissue transcriptome LM47 |
| GSM2695871 |
compensated cirrhotic liver tissue transcriptome LM 57 |
|
| Relations |
| BioProject |
PRJNA393402 |
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