Utjecaj puta dojavljivanja „Notch“ na diferencijaciju stanica hematopoeze

doctoral thesis

• Title (english): The role of “notch” signaling in differentiation of hematopoietic cells
• Author: Mladen Paradžik
• Mentor: Mariastefania Antica (mentor)
• Committee member: Krešo Bendelja (član povjerenstva)
• Committee member: Vesna Benković (član povjerenstva)
• Committee member: Zorana Grubić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2015, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 576 - Cellular and subcellular biology. Cytology

Abstract

Diferencijacija krvnih stanica iz hematopoetskih stanica matica upravljana je mnoštvom čimbenika, od kojih značajnu ulogu imaju transkripcijski čimbenici iz obitelji Ikaros te puta dojavljivanja Notch. Pokazano je kako su čimbenici iz obitelji Ikaros bitni za normalan razvoj limfoidnih loza te da aberantne promjene u njihovoj ekspresiji mogu dovesti do razvoja limfoma kod miševa. Dojavljivanje putem Notcha ključno je za upravljanje smjera diferencijacije hematopoetskih stanica. Dok je značenje u diferencijaciji limfocita T dobro proučeno, uloga navedenih puteva u diferencijaciji limfocita B te mijeloidnoj lozi ostaje slabo istražena, a rezultati kontradiktorni. Cilj rada je ispitati povezanost navedenih puteva kao i njihovu ulogu u diferencijaciji limfoidne i mijeloidne loze pomoću molekularnih metoda poput višestruke lančane reakcije polimerazom na razini pojedinačne stanice, lančane reakcije polimerazom u stvarnom vremenu, bugačenja po Westernu te protočne citometrije. Pokazano je kako čimbenici obitelji Ikaros interagiraju s putem dojavljivanja Notch.Također, Notch ima bitnu ulogu pri diferencijaciji mijeloidnih loza stanica te je bitan čimbenik sprečavanja nastanka apoptoze kod osoba oboljelih od kronične leukemije limfocita B.

Abstract (english)

Differentiation of hematopoietic stem cells into functional mature cells is controlled by a wide array of transcriptional regulators. Ikaros family transcription factors and the Notch signaling pathway are important parts of these processes. It was shown that Ikaros members are essential for the lymphoid development and aberrant changes in their expression could lead to lymphoma expansion in mice. Notch signaling also has a key role in directing the hematopoietic cell fate and its role is mainly confirmed in T lymphocyte development. However, the importance of the Notch signaling in the development of B lymphocytes and myeolid lineage remains poorly understood. The aim of this study is to define the correlation of Ikaros and Notch families in the differentiation of the lymphoid and myeloid lineages, using molecular techniques such as single cell multiplex PCR, real time PCR, Western blotting and flow cytometry. It was confirmed that Ikaros family members interact with the members of Notch signaling pathway. Furthermore, Notch plays a key role in myeloid differentiation and it is important factor in the regulation of the apoptosis in B cell chronic lymphocytic leukemia.

• Keywords: Notch; Ikaros; diferencijacija; hematopoeza; leukemija
• Keywords (english): Notch; Ikaros family; differentiation; hematopoesis; leukemia
• Language: croatian
• URN:NBN: urn:nbn:hr:217:708441
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-05-17 10:00:05