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Series GSE181201 Query DataSets for GSE181201
Status Public on Apr 06, 2022
Title A hierarchical regulatory network ensures stable albumin transcription under various pathophysiological conditions
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Physiologically, albumin is produced by hepatocytes. It remains largely unknown how patients are capable of maintaining essential albumin levels even in the condition of liver failure. Here, we delineate a hierarchical regulatory network that controls albumin transcription under different pathophysiological conditions. The ALB core promoter possesses a TATA box and nucleosome-free area, which allows constitutive binding of RNA Pol II and thus initiation of transcription. In normal conditions, HNF4α and C/EBPα facilitate albumin transcription through binding to its promoter. In severely damaged livers, hepatocellular HNF4α and C/EBPα expression is often inhibited. The absence of HNF4 and C/EBPα increases hedgehog ligand biosynthesis. Hedgehog upregulates FOXA2 expression through transcription factor GLI2 binding to the FOXA2 promoter. Subsequently, FOXA2 maintains albumin expression in the hepatocytes lacking HNF4α and C/EBPα. In patients with massive hepatocyte loss, the expression of albumin is activated in liver progenitor cells. Albumin transcription in these cells is regulated by HNF4α or FOXA2. Taken together, HNF4α, C/EBPα and FOXA2 form a hierarchical regulatory network that ensures stable albumin expression even in pathophysiological conditions.
 
Overall design Mouse primary hepatocytes (MPH) were freshly isolated from three mice: Mouse1, Mouse2, Mouse3. RNA sequencing was performed in MPH with or without HNF4α and C/EBPα siRNA treatment for 48 hours.
 
Contributor(s) Weng H
Citation(s) 35257388
Submission date Jul 30, 2021
Last update date Apr 08, 2022
Contact name Carsten Sticht
Organization name University Heidelberg
Department ZMF
Street address Theodor-Kutzer-Ufer
City Mannheim
ZIP/Postal code 68169
Country Germany
 
Platforms (1)
GPL23479 BGISEQ-500 (Mus musculus)
Samples (12)
GSM5492349 MPH1_siHnf4a siCebpa
GSM5492350 MPH1_siCebpa
GSM5492351 MPH1_siCon
Relations
BioProject PRJNA751052
SRA SRP330566

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE181201_RAW.tar 6.9 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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