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Stem cell fate regulation: computational modeling in the hematopoietic system

Teles, José LU (2012)
Abstract
The ability to sense the surrounding environment and respond to external fluctuations is a fundamental

property of cells, the basic unit of life. Although cells can be very different in their composition and

structure, they all have specialized molecular mechanisms that allow them to adapt to their environment,

by coordinating gene expression and protein production. In this thesis, we focus on a specific type of cells,

called stem cells. These are very important, since they have the potential to generate the different types of

specialized cells that compose the tissues and organs in our body. More specifically, we study hematopoietic

stem cells, which are responsible for producing the... (More)
The ability to sense the surrounding environment and respond to external fluctuations is a fundamental

property of cells, the basic unit of life. Although cells can be very different in their composition and

structure, they all have specialized molecular mechanisms that allow them to adapt to their environment,

by coordinating gene expression and protein production. In this thesis, we focus on a specific type of cells,

called stem cells. These are very important, since they have the potential to generate the different types of

specialized cells that compose the tissues and organs in our body. More specifically, we study hematopoietic

stem cells, which are responsible for producing the different populations of cells that compose our blood

system and execute such different tasks as fighting infections, repairing tissues or transporting oxygen. It

is fundamental for the organism to have the right number of cells, of the right type, at the right time. We

use computational methods to model the molecular mechanisms of gene expression by which individual

cells decide their fate within the complex hierarchy that underlies hematopoiesis.

The papers in this thesis address these mechanisms at different scales of complexity, and as a consequence

use different modeling approaches, supported by experimental data whenever available. In paper

I, we address the structure and dynamical properties of hematopoiesis at the population level, by using

compartmental modeling and rate equations. In papers II and III we use a large amount of experimental

data to infer the architecture of an important gene regulatory circuit. We use deterministic rate equations

to describe how the dynamics of each element of the circuit and their interplay can lead to fate decisions.

Finally, in papers IV and V, we analyze the process of fate decision at the single-cell level, using stochastic

modeling methods. We explore whether commitment to a particular fate involves the coordination of

many genes, and whether different molecular routes can lead to a decision. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Sneppen, Kim, Center for Models of Life, Niels Bohr Institute - University of Copenhagen
organization
publishing date
type
Thesis
publication status
published
subject
keywords
stochastic modeling, dynamical modeling, gene regulation, hematopoiesis, cell fate, stem cells, Fysicumarkivet A:2012:Teles
pages
230 pages
publisher
Computational Biology and Biological Physics , Lund University
defense location
Lundmarksalen
defense date
2012-09-21 13:00
ISBN
978-91-7473-365-5
language
English
LU publication?
yes
id
8bde55d8-29f4-4a57-91f7-13aaa009482c (old id 3046092)
date added to LUP
2012-09-04 12:22:21
date last changed
2016-09-19 08:45:11
@misc{8bde55d8-29f4-4a57-91f7-13aaa009482c,
  abstract     = {The ability to sense the surrounding environment and respond to external fluctuations is a fundamental<br/><br>
property of cells, the basic unit of life. Although cells can be very different in their composition and<br/><br>
structure, they all have specialized molecular mechanisms that allow them to adapt to their environment,<br/><br>
by coordinating gene expression and protein production. In this thesis, we focus on a specific type of cells,<br/><br>
called stem cells. These are very important, since they have the potential to generate the different types of<br/><br>
specialized cells that compose the tissues and organs in our body. More specifically, we study hematopoietic<br/><br>
stem cells, which are responsible for producing the different populations of cells that compose our blood<br/><br>
system and execute such different tasks as fighting infections, repairing tissues or transporting oxygen. It<br/><br>
is fundamental for the organism to have the right number of cells, of the right type, at the right time. We<br/><br>
use computational methods to model the molecular mechanisms of gene expression by which individual<br/><br>
cells decide their fate within the complex hierarchy that underlies hematopoiesis.<br/><br>
The papers in this thesis address these mechanisms at different scales of complexity, and as a consequence<br/><br>
use different modeling approaches, supported by experimental data whenever available. In paper<br/><br>
I, we address the structure and dynamical properties of hematopoiesis at the population level, by using<br/><br>
compartmental modeling and rate equations. In papers II and III we use a large amount of experimental<br/><br>
data to infer the architecture of an important gene regulatory circuit. We use deterministic rate equations<br/><br>
to describe how the dynamics of each element of the circuit and their interplay can lead to fate decisions.<br/><br>
Finally, in papers IV and V, we analyze the process of fate decision at the single-cell level, using stochastic<br/><br>
modeling methods. We explore whether commitment to a particular fate involves the coordination of<br/><br>
many genes, and whether different molecular routes can lead to a decision.},
  author       = {Teles, José},
  isbn         = {978-91-7473-365-5},
  keyword      = {stochastic modeling,dynamical modeling,gene regulation,hematopoiesis,cell fate,stem cells,Fysicumarkivet A:2012:Teles},
  language     = {eng},
  pages        = {230},
  publisher    = {ARRAY(0x9395f40)},
  title        = {Stem cell fate regulation: computational modeling in the hematopoietic system},
  year         = {2012},
}