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Simulations of Astrocyte Induction by Transient Overexpression

Petersson, Jonas LU (2019) FYTK02 20191
Computational Biology and Biological Physics
Department of Astronomy and Theoretical Physics
Abstract
Astrocytes are one of the most common types of cells found in the central nervous system, and they play an important supportive role for neurons and other brain cells. In order to obtain astrocytes for medical or experimental purposes, some protocols enable the production of astrocytes from stem cells, but it is of interest to be able to produce astrocytes from fibroblasts, a cell type found in the skin. By forcing cells to produce specific proteins, it is possible to change a cells specialization, and the goal of this thesis is to model the molecular dynamics that occur during astrocyte formation when starting either from stem or fibroblast cells.

A multi-level model is proposed, with interactions inspired by literature, including... (More)
Astrocytes are one of the most common types of cells found in the central nervous system, and they play an important supportive role for neurons and other brain cells. In order to obtain astrocytes for medical or experimental purposes, some protocols enable the production of astrocytes from stem cells, but it is of interest to be able to produce astrocytes from fibroblasts, a cell type found in the skin. By forcing cells to produce specific proteins, it is possible to change a cells specialization, and the goal of this thesis is to model the molecular dynamics that occur during astrocyte formation when starting either from stem or fibroblast cells.

A multi-level model is proposed, with interactions inspired by literature, including genetic and epigenetic regulations. Model simulations are conducted with overexpression of NFIA and Sox9; and overexpression of NFIA in the presence of LIF, which is predicted to result in that the stem and fibroblast cell states will move into the astrocyte state.

Experimental findings validate the model's predictions. The results are also indicative of new experiments and given more experimental data to optimize the parameters, the model will be able to offer recipes for fine-tuning astrocyte production protocols. (Less)
Popular Abstract (Swedish)
Alla celler i samma kropp har samma genetiska information lagrad i DNA. Olika delar av den genetiska informationen är lagrade i en otillgänglig form. Vilken del av cellens DNA som är tillgänglig avgör sedan vilken specialisering cellen har. Genom att kontrollera vilken information som används kan man omprogrammera celler, till exempel kan en hudcell bli en hjärncell. En metod för att åstadkomma detta är genom att tvinga cellen producera specifika proteiner som startar en omvandlingsprocess.

Astrocyter är en typ av hjärncell som har en stödjande roll i nervsystemet. Forskning har visat att sjukdomar som Alzheimer's och Parkinson kan vara kopplade till defekta astrocyter. Mediciner för att främja astrocyternas funktioner eller... (More)
Alla celler i samma kropp har samma genetiska information lagrad i DNA. Olika delar av den genetiska informationen är lagrade i en otillgänglig form. Vilken del av cellens DNA som är tillgänglig avgör sedan vilken specialisering cellen har. Genom att kontrollera vilken information som används kan man omprogrammera celler, till exempel kan en hudcell bli en hjärncell. En metod för att åstadkomma detta är genom att tvinga cellen producera specifika proteiner som startar en omvandlingsprocess.

Astrocyter är en typ av hjärncell som har en stödjande roll i nervsystemet. Forskning har visat att sjukdomar som Alzheimer's och Parkinson kan vara kopplade till defekta astrocyter. Mediciner för att främja astrocyternas funktioner eller transplantationer av friska astrocyter kan därför hjälpa personer som lider av dessa sjukdomar. Det är en fördel att transplantera astrocyter jämfört med neuroner eftersom astrocyter har en förmåga att migrera till de områden där de behövs. Problemet är att det fortfarande saknas tillräckligt effektiva och säkra metoder för att producera mänskliga astrocyter.

I detta examensarbete utvecklas en datormodell för att simulera processen som sker när stamceller och fibroblaster, en typ av cell som finns i huden, tvingas omvandlas till astrocyter. Modellen lyckas simulera vad som händer när cellen tvingas producera proteinerna NFIA och Sox9, med hjälp av modellen verkar det också gå att optimera de experimentella metoderna som används just nu. (Less)
Please use this url to cite or link to this publication:
author
Petersson, Jonas LU
supervisor
organization
alternative title
Simuleringar av Astrocytinduktion genom Transient Artificiellt Genuttryck
course
FYTK02 20191
year
type
M2 - Bachelor Degree
subject
keywords
astrocyte, overexpression, sox9, nfia, nfib, n-cor
language
English
id
8981059
date added to LUP
2019-06-12 08:42:29
date last changed
2019-06-12 08:42:29
@misc{8981059,
  abstract     = {Astrocytes are one of the most common types of cells found in the central nervous system, and they play an important supportive role for neurons and other brain cells. In order to obtain astrocytes for medical or experimental purposes, some protocols enable the production of astrocytes from stem cells, but it is of interest to be able to produce astrocytes from fibroblasts, a cell type found in the skin. By forcing cells to produce specific proteins, it is possible to change a cells specialization, and the goal of this thesis is to model the molecular dynamics that occur during astrocyte formation when starting either from stem or fibroblast cells.

A multi-level model is proposed, with interactions inspired by literature, including genetic and epigenetic regulations. Model simulations are conducted with overexpression of NFIA and Sox9; and overexpression of NFIA in the presence of LIF, which is predicted to result in that the stem and fibroblast cell states will move into the astrocyte state. 

Experimental findings validate the model's predictions. The results are also indicative of new experiments and given more experimental data to optimize the parameters, the model will be able to offer recipes for fine-tuning astrocyte production protocols.},
  author       = {Petersson, Jonas},
  keyword      = {astrocyte,overexpression,sox9,nfia,nfib,n-cor},
  language     = {eng},
  note         = {Student Paper},
  title        = {Simulations of Astrocyte Induction by Transient Overexpression},
  year         = {2019},
}