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Vpliv aktivacije imunskega sistema (transflamacije) na učinkovitost celičnega reprogramiranja
ID Vrščaj, Eva (Author), ID Ogorevc, Jernej (Mentor) More about this mentor... This link opens in a new window

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Abstract
Za celično reprogramiranje so potrebne spremembe na ravni epigenoma, ki spremenijo dostopnost kromatina in povečajo epigenetsko plastičnost. Na epigenetske modifikacije med reprogramiranjem vpliva tudi indukcija prirojene imunosti. Ta proces se imenuje transflamacija. Transflamacija je posredovana preko tollu podobnih receptorjev, ki inducirajo NF-κB, ta pa vpliva na spremembe v izražanju genov za encime, ki so vključeni v modifikacije kromatina. Transflamacija inducira tudi glikolitični preklop, ki ima pomembno vlogo pri reprogramiranju celic in tudi nadalje inducira epigenetske modifikacije. Pri reprogramiranju celic z uporabo retrovirusov transflamacijo inducira virusna dsRNA preko TLR3. Vnos transkripcijskih dejavnikov reprogramiranja z neintegrativnimi metodami (npr. mRNA, proteini) ne povzroča integracije tuje DNA, kot na primer pri retrovirusih, vendar velja za manj učinkovito, najverjetneje ravno zaradi odsotnosti transflamacije. Pri uporabi nekaterih metod je zato potrebno dodatno stimulirati prirojeno imunost, ki pospeši spremembe v dostopnosti kromatina in tako poveča učinkovitost reprogramiranja. Aktivacija prirojene imunosti pa lahko vpliva tudi na transdiferenciacijo v rakavih tkivih, kar lahko vodi do pro- ali proti-tumorskega učinka. Namen tega dela je, pregled obstoječih raziskav o pomenu transflamacije in ocena njenega aplikativnega pomena.

Language:Slovenian
Keywords:reprogramiranje, transdiferenciacija, epigenetske modifikacije, transflamacija, TLR3, glikolitični preklop, rak
Work type:Bachelor thesis/paper
Typology:2.11 - Undergraduate Thesis
Organization:BF - Biotechnical Faculty
Year:2023
PID:20.500.12556/RUL-147611 This link opens in a new window
COBISS.SI-ID:158354691 This link opens in a new window
Publication date in RUL:10.07.2023
Views:925
Downloads:79
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Secondary language

Language:English
Title:Effect of transflammation on cell reprogramming efficiency
Abstract:
Cellular reprogramming requires changes at the epigenome level that modify chromatin accessibility and enhance epigenetic plasticity. During the reprogramming process, epigenetic alterations are influenced by the induction of innate immunity, a process known as transflammation. Transflammation is mediated via toll-like receptors , which subsequently induce NF-κB. NF-κB impacts the expression of genes related to chromatin modifications. Transflammation also induces a glycolytic switch, which plays an important role in cell reprogramming and additionally prompts epigenetic modifications. When cells are reprogrammed using retroviruses, transflammation is induced by viral dsRNA through TLR3. Unlike retroviruses, the introduction of reprogramming transcription factors using non-integrative methods (e.g., mRNA, proteins), does not leave any trace at the DNA level, but is considered less efficient, possibly because the lack of transflammation. Therefor, some methods require additional stimulation of innate immunity to accelerate changes in chromatin accessibility and increase the efficiency of reprogramming. Activation of innate immunity can also induce transdifferentiation in cancerous tissues, which may result in a pro- or anti-tumor effect. The objective of this work is to review existing research on the significance of transflammation and evaluate its practical implications.

Keywords:reprogramming, transdifferentiation, epigenetic modifications transflammation, TLR3, glycolytic switch, cancer

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