Intestinal stem cells in Nothobranchius furzeri
Intestinal stem cells in Nothobranchius furzeri
Disciplines
Biology (60%); Medical-Theoretical Sciences, Pharmacy (40%)
Keywords
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Aging,
Intestine,
Homeostasis,
Nothobranchius furzeri,
Adult Stem Cells,
Tissue Biology
Aging can be defined as the product of cellular decline and tissue dysfunction over time. Tissue homeostasis, which is the maintenance of proper tissue structure by regulating the balance between cell proliferation and cell death, is critically involved in aging processes Stem cells are pivotal players in this dynamic process. They may become exhausted throughout life meaning that their numbers decline and/or their potential to give rise to differentiating cells decreases. Stem cells of the intestinal tract are one of the best-studied stem cells. Intestinal stem cells (ISCs) were predominately studied in rodents and ISCs were found to give rise to all cell types of the intestinal epithelium. Further, it was discovered which molecular factors are responsible for ISC maintenance, proliferation and regeneration. It would be highly interesting to study aging of ISCs during the entire lifespan of animals. However, mice are rather long-lived whereas a short-lived model system would be preferred. In this project, we will use the novel aging research model system Nothobranchius furzeri in order to study aging of ISCs. Its lifetime of 10 weeks is the shortest life span of all vertebrate model systems known so far. In the proposed project, we aim to address the following questions: a) How is the intestinal tract of N. furzeri structured? This is a prerequisite because information of intestinal architecture is lacking. b) Where are the ISCs located? c) Which molecular markers are involved in ISC regulation? Here, we will test factors known from mammals to be specific for ISCs and probe for their presence in N. furzeri. d) Having accomplished these tasks, we have finally the pre-requisites at hand to go on and study possible changes in number and proliferative capacity of ISCs during aging of the fish. Most of the methods we intend to apply are established standard techniques and include anatomy, histology, molecular and immunological methods to detect proteins and nucleic acids on sections. In addition, labelled components of DNA will be administered to live fish where they will become incorporated into DNA during cell divisions and thus be informative of the proliferative status of cells. With the proposed project, we will gain basic insights in the aging process of intestinal stem cells. The obtained information will enable us to perform follow-up studies where we will learn more about the molecular mechanisms that influence aging of ISCs. Ultimately, we might be able to influence ISCs such that they maintain a youthful state over longer periods thus to retard aging processes in the intestine. We expect that findings of studies on ISCs of N. furzeri will be relevant for humans and may contribute to development of drugs to ameliorate intestinal homeostasis and regeneration in aging and disease.
Research Output
- 86 Citations
- 7 Publications
- 1 Policies
- 1 Disseminations
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2021
Title Analysis of Methylation Dynamics Reveals a Tissue-Specific, Age-Dependent Decline in 5-Methylcytosine Within the Genome of the Vertebrate Aging Model Nothobranchius furzeri DOI 10.3389/fmolb.2021.627143 Type Journal Article Author Zupkovitz G Journal Frontiers in Molecular Biosciences Pages 627143 Link Publication -
2022
Title Emerin prevents BAF-mediated aggregation of lamin A on chromosomes in telophase to allow nuclear membrane expansion and nuclear lamina formation DOI 10.1091/mbc.e22-01-0007 Type Journal Article Author Snyers L Journal Molecular Biology of the Cell Link Publication -
2022
Title CX-5461 causes nucleolar compaction, alteration of peri- and intranucleolar chromatin arrangement, an increase in both heterochromatin and DNA damage response DOI 10.1038/s41598-022-17923-4 Type Journal Article Author Snyers L Journal Scientific Reports Pages 13972 Link Publication -
2024
Title Comparative transcriptomics coupled to developmental grading via transgenic zebrafish reporter strains identifies conserved features in neutrophil maturation DOI 10.1038/s41467-024-45802-1 Type Journal Article Author Kirchberger S Journal Nature Communications Pages 1792 Link Publication -
2018
Title Histone deacetylase 1 expression is inversely correlated with age in the short-lived fish Nothobranchius furzeri DOI 10.1007/s00418-018-1687-4 Type Journal Article Author Zupkovitz G Journal Histochemistry and Cell Biology Pages 255-269 Link Publication -
2018
Title Nucleolus and chromatin DOI 10.1007/s00418-018-1696-3 Type Journal Article Author Schöfer C Journal Histochemistry and Cell Biology Pages 209-225 Link Publication -
2018
Title Phylogenetic analysis and expression profiling of the Klotho gene family in the short-lived African killifish Nothobranchius furzeri DOI 10.1007/s00427-018-0619-6 Type Journal Article Author Zupkovitz G Journal Development Genes and Evolution Pages 255-265 Link Publication
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2019
Title 3R Type Contribution to new or Improved professional practice
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2018
Title Interview for national news Type A magazine, newsletter or online publication