M. Sc. thesis
Tajda Klobučar (Author), Uroš Petrovič (Reviewer), Jernej Ogorevc (Mentor), Jernej Ogorevc (Thesis defence commission member), Simão José Teixeira da Rocha (Thesis defence commission member), Mojca Narat (Thesis defence commission member), Uroš Petrovič (Thesis defence commission member), Simão José Teixeira da Rocha (Co-mentor)

Abstract

Induced pluripotent stem cells (iPSCs) can be obtained from somatic cells through a dynamic process of reprogramming and represent an important step towards personalized regenerative medicine. Unfortunately, through available reprogramming protocols, iPSCs still acquire several genetic and epigenetic aberrations. A specific group of common epigenetic defects are so-called imprinting errors. Genomic imprinting is an epigenetic phenomenon causing monoallelic expression of some genes in a parent-of-origin-specific manner. This unique expression pattern is controlled by differential DNA methylation at imprinting control regions (ICRs). The preservation of imprinting status is a prerequisite for the safe use of iPSCs in disease modelling and regenerative medicine. While several reports have described abnormal DNA methylation at ICRs, the lack of comprehensive analysis limits the understanding of their source. With the use of a novel high-throughput method for assessing DNA methylation at multiple ICRs (IMPLICON), we obtained an overview of common methylation discrepancies at ICRs in newly generated female and male murine iPSCs. We were able to show that gender of donor cells, as well as culture conditions used for reprogramming, are important factors in the acquisition of genomic imprinting defects in iPSCs.

Keywords

induced pluripotent stem cells;genomic imprinting;DNA methylation;

Data

Language: English
Year of publishing:
Typology: 2.09 - Master's Thesis
Organization: UL BF - Biotechnical Faculty
Publisher: [T. Klobučar]
UDC: 602.9:591.81(043.2)
COBISS: 23562755 Link will open in a new window
Views: 541
Downloads: 126
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Other data

Secondary language: Slovenian
Secondary title: Karakterizacija napak v genomskem vtisnjenju med reprogramiranjem mišjih celic
Secondary abstract: Inducirane pluripotentne matične celice (ang. iPSC) pridobimo iz somatskih celic v dinamičnem procesu celičnega reprogramiranja in kot take predstavljajo pomemben korak v smer personalizirane regenerativne medicine. Žal s trenutno dostopnimi protokoli reprogramiranja celice pridobijo veliko genetskih in epigenetskih napak. Posebna skupina pogostih epigenetskih napak se pojavlja pri genomsko vtisnjenih genih. Genomsko vtisnjenje je epigenetski pojav, ki opisuje starševsko-odvisno izražanje genov iz samo enega starševskega alela. Takšen vzorec izražanja je nadzorovan z mehanizmom metilacije DNA na kontrolnih regijah genomskega vtisnjenja (ang. ICR). Stabilno genomsko vtisnjenje je predpogoj za varno uporabo iPSC pri bolezenskih modelih in v regenerativni medicini. Kljub več objavam, ki opisujejo nepravilno metilacijo DNA na ICR, celostne analize napak genomskega vtisnjenja še niso bile narejene, kar omejuje razumevanje izvora le-teh. Z uporabo nove metode za analizo metilacije DNA na več kontrolnih regijah hkrati (IMPLICON) smo pridobili vpogled v pogostost nepravilne metilacije DNA na več ICR v novo pridobljenih moških in ženskih mišjih iPSC. Pokazali smo, kako pomembna dejavnika sta spol darovanih (somatskih) celic in pogoji gojenja pri pojavu napak genomskega vtisnjenja pri induciranih pluripotentnih matičnih celicah.
Secondary keywords: inducirane pluripotentne matične celice;genomsko vtsinjenje;DNA metilacija;
Type (COBISS): Master's thesis/paper
Study programme: 0
Embargo end date (OpenAIRE): 2021-07-17
Thesis comment: Univ. v Ljubljani, Biotehniška fak., Študij biotehnologije
Pages: X, 64 f., [5] f. pril.
ID: 11915331