 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 06, 2023 |
| Title |
Hepatocytes reprogram liver macrophages involving control of TGF-β activation, influencing liver regeneration and injury |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
We aimed at elucidating the molecular and cellular crosstalk how inflammation controls proper liver regeneration. Therefore populations of liver macrophages were studied in genetically different mouse models after PHx using flow cytometry and single cell sequencing. Intercellular communication was examined in vitro, combining proteomics and transcriptomics. We observed marked changes in the composition of macrophage populations in the liver during the regeneration process. A F4/80+/CD11bhigh/CD14high macrophage population that is recruited in a CCR2 dependent manner increased rapidly after PHx. The polarization of the recruited macrophages differs from that under homeostatic conditions , but reappears during the late phase of the process. Proteomics, secretomics, and transcriptomics show that hepatocyte derived signals reduce the availability of active TGFb and thereby affect macrophage polarization and function towards the aforementioned phenotype. Depleting the TGFb type II receptor in myeloid cells phenocopies the hepatocyte-mediated macrophage polarization in vitro and in vivo. Moreover, disrupting TGFb signal transduction in macrophages is associated with increased expression of regeneration-relevant cytokines such as IL-6, reduced resection-induced liver damage and prolongated proliferation phase of hepatocytes in mice. Conclusion: Upon liver injury, hepatocytes have a major influence on the activation state of recruited liver macrophages by regulating the availability of active TGFb and TGFb induces a macrophage phenotype that aggravates injury. Ultimately, this mechanism influences the extent of intervention-induced liver injury as well as the proliferation phase during liver regeneration.
In this data set, we investigated the influence of hepatocytes on co-cultured macrophages and vice versa.
|
| |
|
| Overall design |
The RNA expression of primary hepatocytes and BMDM were analysed. Therefore 4 different conditions (mono- vs. co-culture, hepatocytes and macrophages) with 5 replicas each were measured to detect the impact of hepatocytes on macrophages and vice versa.
|
| |
|
| Contributor(s) |
Wolf SD, Ehlting C, Mueller-Dott S, Poschmann G, Petzsch P, Lautwein T, Wang S, Helm B, Schilling M, Saez-Rodriguez J, Vucur M, Stühler K, Köhrer K, Tacke F, Dooley S, Klingmüller U, Luedde T, Bode JG |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Apr 25, 2022 |
| Last update date |
Jul 07, 2023 |
| Contact name |
Stephanie Daniela Wolf |
| E-mail(s) |
stephanie.wolf@uni-duesseldorf.de
|
| Organization name |
Universitätsklinikum Düsseldorf
|
| Department |
Gastroenterology, Hepatology and Infectious Disease
|
| Street address |
Moorenstrasse 5, Geb. 13.58 Raum 04
|
| City |
Düsseldorf |
| State/province |
NRW |
| ZIP/Postal code |
40225 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
|
| Samples (20)
|
| GSM6064778 |
Hepatocytes_co-culture_biological rep4 |
| GSM6064779 |
Hepatocytes_co-culture_biological rep5 |
| GSM6064780 |
Marcrophages_co-culture_biological rep1 |
| GSM6064781 |
Marcrophages_co-culture_biological rep2 |
| GSM6064782 |
Marcrophages_co-culture_biological rep3 |
| GSM6064783 |
Marcrophages_co-culture_biological rep4 |
| GSM6064784 |
Marcrophages_co-culture_biological rep5 |
| GSM6064785 |
Hepatoyctes_mono-culture_biological rep1 |
| GSM6064786 |
Hepatoyctes_mono-culture_biological rep2 |
| GSM6064787 |
Hepatoyctes_mono-culture_biological rep3 |
| GSM6064788 |
Hepatoyctes_mono-culture_biological rep4 |
| GSM6064789 |
Hepatoyctes_mono-culture_biological rep5 |
| GSM6064790 |
Macrophages_mono-culture_biological rep1 |
| GSM6064791 |
Macrophages_mono-culture_biological rep2 |
| GSM6064792 |
Macrophages_mono-culture_biological rep3 |
| GSM6064793 |
Macrophages_mono-culture_biological rep4 |
| GSM6064794 |
Macrophages_mono-culture_biological rep5 |
|
| Relations |
| BioProject |
PRJNA831837 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE201467_RAW.tar |
25.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...