Thalheim, Torsten, Siebert, Susann, Quaas, Marianne, Herberg, Maria, Schweiger, Michal R., Aust, Gabriela and Galle, Joerg (2021). Epigenetic Drifts during Long-Term Intestinal Organoid Culture. Cells, 10 (7). BASEL: MDPI. ISSN 2073-4409

Full text not available from this repository.

Abstract

Organoids retain the morphological and molecular patterns of their tissue of origin, are self-organizing, relatively simple to handle and accessible to genetic engineering. Thus, they represent an optimal tool for studying the mechanisms of tissue maintenance and aging. Long-term expansion under standard growth conditions, however, is accompanied by changes in the growth pattern and kinetics. As a potential explanation of these alterations, epigenetic drifts in organoid culture have been suggested. Here, we studied histone tri-methylation at lysine 4 (H3K4me3) and 27 (H3K27me3) and transcriptome profiles of intestinal organoids derived from mismatch repair (MMR)-deficient and control mice and cultured for 3 and 20 weeks and compared them with data on their tissue of origin. We found that, besides the expected changes in short-term culture, the organoids showed profound changes in their epigenomes also during the long-term culture. The most prominent were epigenetic gene activation by H3K4me3 recruitment to previously unmodified genes and by H3K27me3 loss from originally bivalent genes. We showed that a long-term culture is linked to broad transcriptional changes that indicate an ongoing maturation and metabolic adaptation process. This process was disturbed in MMR-deficient mice, resulting in endoplasmic reticulum (ER) stress and Wnt activation. Our results can be explained in terms of a mathematical model assuming that epigenetic changes during a long-term culture involve DNA demethylation that ceases if the metabolic adaptation is disturbed.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Thalheim, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siebert, SusannUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Quaas, MarianneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herberg, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schweiger, Michal R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aust, GabrielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Galle, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-576698
DOI: 10.3390/cells10071718
Journal or Publication Title: Cells
Volume: 10
Number: 7
Date: 2021
Publisher: MDPI
Place of Publication: BASEL
ISSN: 2073-4409
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DNA HYPER-METHYLATION; STEM-CELL; IN-VITRO; CANCER; MOUSE; HETEROGENEITY; ACTIVATIONMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/57669

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item