<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Identification of a functional mRNA-miRNA network in mTEC\r\ndevelopment"^^ . "The adaptive immune system with its diversity of immune cells and their\r\nreceptors allows an effective fight against a plethora of pathogens. The\r\ndevelopment of T cells is taking place in the thymus, where it undergoes two\r\nselections that is immensely important to ensure self-tolerance. For those two\r\nstrictly regulated selection processes there are two major cell components\r\nbeing responsible for that called cortical thymic epithelial cells (cTEC) and\r\nmedullary thymic epithelial cells (mTEC). MTECs are playing an important role\r\nfor the prevention of autoimmune diseases as they express self-antigens to\r\nthe maturing T cells. The current knowledge describes basically the function\r\nof cTECs and mTECs, the development of a stem cell to mTEC, the\r\ninvolvement of molecular mechanisms which influences the development of\r\nthymus and mTECs, still not in every single details. To date molecular details\r\nare still missing how an immature mTEC develops to a mature mTEC,\r\nespecially molecular mechanisms, which influence the maturation and what\r\ncontrols each single step to its final maturation. Previous researches have\r\nfound in the immature mTECs four new subpopulations present in fetal and\r\nembryonic mTECs, which have not been shown in adult mice. Until now only\r\na handful of microRNAs (miRNAs) have been found to play a role in mTECs,\r\nbut no miRNAs have been founds to play an active role in the maturation\r\nprocess of mTECs. The scope of this doctorate thesis was to characterise the\r\nfour subpopulations in adult mice with the help of mRNA and miRNA\r\nmicroarray analyses. With the help of the mRNA gene arrays we could\r\ndecipher a lineage sequence within the four subpopulations stating that Sca1\r\nas the most progenitor population Sca-1 < DP < CD24 < DN. According to the\r\nanalyses DN was the closest cell population to mature mTECs, probably one\r\nstep before coming a mature mTEC. Thereupon we used bioinformatics to\r\nfilter the most prominent miRNAs, which might play an important role in the\r\ndevelopment of the four subpopulations. Those miRNAs were verified by\r\nusing a SCID mouse model, which emulates the dynamic development of the\r\nfour subpopulations. Subsequently we inhibited or overexpressed those\r\nmiRNA candidates in freshly isolated mTECs to see their influence of the\r\ndevelopment of the four subpopulations. At the end we found 11 promising\r\nmiRNAs that play a role in the maturation of the four subgroups. This finding\r\nresulted in a deeper search for possible mRNA interaction partners for those\r\nmiRNA candidates. After investigating 35 mRNAs we found 4 miRNA-mRNA\r\ninteractions, which have not been described in the mTEC development\r\nbefore. Following miRNA-mRNA networks have been found: miR-34a\r\ninteracts with Foxp1, Mir-125b-5p with Bak1 and Mapk14, miR-125a-3p with\r\nFam83e. This thesis completes the understanding of the four subpopulations\r\nin adult mice as well discovered 4 new miRNA-mRNA interactions, which are\r\nimportant for the maturation of the four subpopulations. With this newly gained\r\nknowledge we can apply it to the human thymus and their mTEC development\r\nwith the hope to boost the thymus function after chemotherapy and organ\r\ntransplantations."^^ . "2018" . . . . . . . "Kaiyong"^^ . "Li"^^ . "Kaiyong Li"^^ . . . . . . "Identification of a functional mRNA-miRNA network in mTEC\r\ndevelopment (PDF)"^^ . . . "Thesis_KaiyongLi.pdf"^^ . . . "Identification of a functional mRNA-miRNA network in mTEC\r\ndevelopment (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Identification of a functional mRNA-miRNA network in mTEC\r\ndevelopment (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Identification of a functional mRNA-miRNA network in mTEC\r\ndevelopment (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Identification of a functional mRNA-miRNA network in mTEC\r\ndevelopment (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Identification of a functional mRNA-miRNA network in mTEC\r\ndevelopment (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #25272 \n\nIdentification of a functional mRNA-miRNA network in mTEC \ndevelopment\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .