|
|
Research of epigenetic aspects of hematopoietic and spermatogenesis stem cells.
Hybešová, Michaela ; Pimková, Kristýna (advisor) ; Děd, Lukáš (referee)
Stem cell differentiation is controlled by coordinated regulation of gene transcription. One of the regulatory factors is the loosening of chromatin and the accessibility of DNA to transcription factors. Chromatin remodeling is mediated by remodeling complexes. The ISWI chromatin remodeling ATPase Smarca5 (S5) is an important factor of remodeling complexes. It is a highly conserved chromatin-remodeling factor forming a catalytic subunit that can be found in several oligosubunit complexes. In these complexes, it actively regulates nucleosome structure and remodeling during DNA replication, repair and transcription. S5 has been identified as a key protein in embryonic development. Its deficiency leads to defects in hematopoiesis and male genital development. In the presented study, we focused on the role of S5 in hematopoiesis and spermatogenesis. Using a mouse model with transgenic expression of S5, co-immunoprecipitation and mass spectrometry, we identified S5 complexes in hematopoietic and testicular cells. We also studied the phenotypic consequences of S5 deficiency in mouse testes and found that it leads to impaired sperm development and male sterility. Using transcriptomic and proteomic analysis, we identified several molecular programs that could lead to reproductive disorders. Our work...
|
|
|
Cellular and molecular basis of a skin regeneration in amphibians and mammals
Hybešová, Michaela ; Krylov, Vladimír (advisor) ; Jendelová, Pavla (referee)
Wound healing of skin in mammals and its regeneration in Amphibians are crucial biomedicine topics in the last few decades. The most important aspect in humans is the scrarring proccess and the effort to substitute it with the regeneration producing functional and differentiated tissues. To modulate the formation of scar it is neccessary to compare both proccesses. The core animal model is axolotl (Caudata) where regeneration takes place during whole lifespam. On the other hand, in frogs (Anurans) this phenomenon is restricted up to metamorphosis. After metamorphosis, the immune system of Anurans is similar if compared to mammals. Similarly, the transition from early embryonic development in mammals, where the fetus was able to completely regenerate damaged tissue to an adult type of healing, goes hand-in-hand with the development of the immune system and structural differentiation of damaged tissue. Thus, the inflammatory cells and their regulation, the formation of ECM, which includes fibroblast proliferation, and the production of appropriate cytokines are key factors that distinguish the process of healing with and without scarring.
|
guest ::
