title: Identification of a functional mRNA-miRNA network in mTEC  development
creator: Li, Kaiyong
subject: ddc-570
subject: 570 Life sciences
description: The adaptive immune system with its diversity of immune cells and their  receptors allows an effective fight against a plethora of pathogens. The  development of T cells is taking place in the thymus, where it undergoes two  selections that is immensely important to ensure self-tolerance. For those two  strictly regulated selection processes there are two major cell components  being responsible for that called cortical thymic epithelial cells (cTEC) and  medullary thymic epithelial cells (mTEC). MTECs are playing an important role  for the prevention of autoimmune diseases as they express self-antigens to  the maturing T cells. The current knowledge describes basically the function  of cTECs and mTECs, the development of a stem cell to mTEC, the  involvement of molecular mechanisms which influences the development of  thymus and mTECs, still not in every single details. To date molecular details  are still missing how an immature mTEC develops to a mature mTEC,  especially molecular mechanisms, which influence the maturation and what  controls each single step to its final maturation. Previous researches have  found in the immature mTECs four new subpopulations present in fetal and  embryonic mTECs, which have not been shown in adult mice. Until now only  a handful of microRNAs (miRNAs) have been found to play a role in mTECs,  but no miRNAs have been founds to play an active role in the maturation  process of mTECs. The scope of this doctorate thesis was to characterise the  four subpopulations in adult mice with the help of mRNA and miRNA  microarray analyses. With the help of the mRNA gene arrays we could  decipher a lineage sequence within the four subpopulations stating that Sca1  as the most progenitor population Sca-1 < DP < CD24 < DN. According to the  analyses DN was the closest cell population to mature mTECs, probably one  step before coming a mature mTEC. Thereupon we used bioinformatics to  filter the most prominent miRNAs, which might play an important role in the  development of the four subpopulations. Those miRNAs were verified by  using a SCID mouse model, which emulates the dynamic development of the  four subpopulations. Subsequently we inhibited or overexpressed those  miRNA candidates in freshly isolated mTECs to see their influence of the  development of the four subpopulations. At the end we found 11 promising  miRNAs that play a role in the maturation of the four subgroups. This finding  resulted in a deeper search for possible mRNA interaction partners for those  miRNA candidates. After investigating 35 mRNAs we found 4 miRNA-mRNA  interactions, which have not been described in the mTEC development  before. Following miRNA-mRNA networks have been found: miR-34a  interacts with Foxp1, Mir-125b-5p with Bak1 and Mapk14, miR-125a-3p with  Fam83e. This thesis completes the understanding of the four subpopulations  in adult mice as well discovered 4 new miRNA-mRNA interactions, which are  important for the maturation of the four subpopulations. With this newly gained  knowledge we can apply it to the human thymus and their mTEC development  with the hope to boost the thymus function after chemotherapy and organ  transplantations.
date: 2018
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/25272/1/Thesis_KaiyongLi.pdf
identifier: DOI:10.11588/heidok.00025272
identifier: urn:nbn:de:bsz:16-heidok-252720
identifier:   Li, Kaiyong  (2018) Identification of a functional mRNA-miRNA network in mTEC development.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/25272/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng