Cell lineage tracing in the human pancreas
Background and aims: The human pancreas is normally proliferatively quiescent; however loss of cells gives a rapid regenerative response to restore a functionally healthy tissue mass. The mechanism for this is unclear and to date research has failed to identify a definitive pancreatic stem cell. Cel...
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| Formato: | L3 |
| Lenguaje: | Inglés sueco |
| Publicado: |
SLU/Dept. of Biomedical Sciences and Veterinary Public Health (until 231231)
2007
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| Materias: |
| _version_ | 1855571867848409088 |
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| author | Engqvist, Julia |
| author_browse | Engqvist, Julia |
| author_facet | Engqvist, Julia |
| author_sort | Engqvist, Julia |
| collection | Epsilon Archive for Student Projects |
| description | Background and aims: The human pancreas is normally proliferatively quiescent; however loss of cells gives a rapid regenerative response to restore a functionally healthy tissue mass. The mechanism for this is unclear and to date research has failed to identify a definitive pancreatic stem cell. Cell lineage analyses are possible in animals by labelling cells with radioactive tags or genetic markers, but this is not feasible in humans. Current human studies rely on stem cell markers, thus there is a need to develop a better technique to track, isolate and identify cells of related origin. Mitochondrial DNA mutations amass naturally within our cells as we age. Therefore, cells formed by division of a stem cell carrying mutated mitochondrial DNA should, given a qualitative assay, permit the progeny of this cell to be traced.
Methods and results: Mitochondrial DNA mutations often result in a defect in the mitochondrial DNA-encoded protein cytochrome c oxidase, and can be identified using a histochemical stain. Individual mutant patches were studied by staining serial sections of normal pancreas. This revealed the presence of clonal units of cells, strong evidence that pancreatic cells within each patch are derived from a common progenitor. We tried to show that these cells are normal in synthetic and proliferative function, although this showed that the mitochondrial DNA mutated cells didn't have normal synthetic function. However this did not negate our evidence of clonal proliferation.
Conclusion: This novel means of tracing patterns of cell division and migration in human tissues is suitable for finding how cells proliferate and move in the human pancreas, and with continued work it might be useful as a marker for other changes e.g. pre-cancerous lesions. |
| format | L3 |
| id | RepoSLU11410 |
| institution | Swedish University of Agricultural Sciences |
| language | Inglés swe |
| publishDate | 2007 |
| publishDateSort | 2007 |
| publisher | SLU/Dept. of Biomedical Sciences and Veterinary Public Health (until 231231) |
| publisherStr | SLU/Dept. of Biomedical Sciences and Veterinary Public Health (until 231231) |
| record_format | eprints |
| spelling | RepoSLU114102017-10-06T07:34:24Z Cell lineage tracing in the human pancreas Stamcellsmarkörer i pankreas Engqvist, Julia pancreas cytochrome c oxidase mitochondrial DNA stem cell Background and aims: The human pancreas is normally proliferatively quiescent; however loss of cells gives a rapid regenerative response to restore a functionally healthy tissue mass. The mechanism for this is unclear and to date research has failed to identify a definitive pancreatic stem cell. Cell lineage analyses are possible in animals by labelling cells with radioactive tags or genetic markers, but this is not feasible in humans. Current human studies rely on stem cell markers, thus there is a need to develop a better technique to track, isolate and identify cells of related origin. Mitochondrial DNA mutations amass naturally within our cells as we age. Therefore, cells formed by division of a stem cell carrying mutated mitochondrial DNA should, given a qualitative assay, permit the progeny of this cell to be traced. Methods and results: Mitochondrial DNA mutations often result in a defect in the mitochondrial DNA-encoded protein cytochrome c oxidase, and can be identified using a histochemical stain. Individual mutant patches were studied by staining serial sections of normal pancreas. This revealed the presence of clonal units of cells, strong evidence that pancreatic cells within each patch are derived from a common progenitor. We tried to show that these cells are normal in synthetic and proliferative function, although this showed that the mitochondrial DNA mutated cells didn't have normal synthetic function. However this did not negate our evidence of clonal proliferation. Conclusion: This novel means of tracing patterns of cell division and migration in human tissues is suitable for finding how cells proliferate and move in the human pancreas, and with continued work it might be useful as a marker for other changes e.g. pre-cancerous lesions. Cellerna i bukspottkörteln hos människa är normalt inte proliferativa, om dessa celler skadas är regenerationen snabb. Den bakomliggande mekanismen är inte känd men det innebär att pankreas funktion bibehålls. Forskning har ännu inte kunnat identifiera en definitiv stamcell i pankreas. I djurförsök är det möjligt att använda radioaktiva eller genetiska markörer för att följa cellinjer, vilket inte är möjligt i humanforskning utan där används istället stamcellsmarkörer. Det finns därför ett behov att utveckla bättre teknik för att kunna följa, isolera och identifiera celler av samma ursprung (stamceller). Kvalitativ teknik skulle kunna möjliggöra kartläggning av ursprunget till celler, vilka härstammar från stamceller med mutationer, eftersom mutationer av mitokondriell-DNA ackumuleras natruligt i våra celler allt eftersom vi åldras. Eftersom proteinet cytokrom c oxidas kodas från mitokondriellt-DNA uppstår ofta defekter i cytokrom c oxidas om DNA:t är muterat. I den redovisade studien undersöktes muterade områden i normal pankreas där klonala grupper med celler kunde påvisas med hjälp av immunohistokemi avseende förekomsten av cytokrom c oxidas. Dessa grupper av celler har troligtvis samma ursprung. I studien försökte vi visa att dessa celler även uppvisade normal funktion, även vad gäller proliferationskapacitet. Undersökningen visade dock att celler med muterat mitokondriellt-DNA inte har normal funktion. Tekniken att spåra cellers delning och rörelse i human vävnad är användbar för att följa hur celler prolifererar och förflyttar sig i pankreas. Fortsatta studier inom området skulle kunna identifiera markörer för att påvisa förändringar i pankreasceller, som exempelvis förstadier till cancer. SLU/Dept. of Biomedical Sciences and Veterinary Public Health (until 231231) 2007 L3 eng swe https://stud.epsilon.slu.se/11410/ |
| spellingShingle | pancreas cytochrome c oxidase mitochondrial DNA stem cell Engqvist, Julia Cell lineage tracing in the human pancreas |
| title | Cell lineage tracing in the human pancreas |
| title_full | Cell lineage tracing in the human pancreas |
| title_fullStr | Cell lineage tracing in the human pancreas |
| title_full_unstemmed | Cell lineage tracing in the human pancreas |
| title_short | Cell lineage tracing in the human pancreas |
| title_sort | cell lineage tracing in the human pancreas |
| topic | pancreas cytochrome c oxidase mitochondrial DNA stem cell |