Współtwórca:

Bużańska, Leonora ( Promotor)

Wydawca:

Instytut Medycyny Doswiadczalnej i Klinicznej im. M. Mossakowskiego PAN

Miejsce wydania:

Warsaw

Opis:

Biblliografia zawiera 40 pozycji. ; 95 s.: il., wykr.tabl., fotogr. ; 30 cm.

Uzyskany tytuł:

PhD

Stopień studiów:

2

Dyscyplina :

medical biology

Instytucja nadająca tytuł:

Mossakowski Medical Research Center PAS

Abstrakt:

Human induced pluripotent stem cells (hiPSC) generated from somatic cells through genetic reprogramming influenced greatly development of basic research in regenerative medicine as well as in vitro toxicology and pharmacology field. The progress in the “safemethods” of hiPSC generation (without the integration of the transgene into the host genome, eg., mRNA, recombinant proteins, miRNA’s, episomal vectors) gave an opportunity to use this cells in personalized cell therapy. In addition, the hiPSC serve as ethically non-controversial in vitro model of early human development which is an alternative to the model of human embryonic stem cells (hESC). The cycle of publications chosen for the theses investigates the influence of stimulation of mitochondrial biogenesis on the early stages of hiPSC neural differentiation. In this study, neural differentiation of hiPSC resulted in obtaining three distinct cells populations: neural stem cells (NSC), early neural progenitors (eNP), and neural progenitors (NP) however, the population of eNP cells has been characterized for the first time. Analysis of the gene and protein expression have shown that NSC, eNP and NP cell populations were significantly different in the level of unique markers for early neural development. The obtained cell populations were investigated for their sensitivity to compounds stimulating the mitochondrial biogenesis: Pyrroloquinoline quinone (PQQ) or idebenone (IDB), which were added independently. The results revealed significant changes in the cells viability, free radical level (ROS) and mitochondrial membrane potential (ΔΨm) upon the treatment with PQQ and IDB in all tested populations. The expression of genes related with mitochondrial biogenesis regulation: NRF1, PPARGC1A andTFAM were also significantly different. However exclusively at the eNP stage, after incubation with PQQ and IDB, all markers indicating stimulation of mitochondrial biogenesis were significantly elevated.This included upregulation of NRF1, PPARGC1A, TFAM gene expression, increased number of copies of mitochondrial DNA (mtDNA) and significant elevation of expression of proteinsimportant for mitochondrial function: COX-1 and SDHA. Gene expression analysis of neural differentiation upon PQQ treatment revealed in NSC and eNP stages of developmentsimultaneous increase in expression of PPARGC1A (main regulator of mitochondrial biogenesis) and astrocyte marker GFAPaccompanied with repression of the neuronal marker MAP2. IDB in all stages of development yielded a similar effect with the exception of eNP, where stimulation of theexpression of both GFAP and MAP2was observed, although the increase in GFAP expression was higher. The above data demonstrate the existence of developmental “window of sensitivity" for investigated factors (PQQ, IDB) inducing mitochondrial biogenesis at eNP stage of development and the possibility of influencing of the neural differentiation pathways via PQQ and IDB in favour of astrocytic fate.

Szczegółowy typ zasobu:

PhD Dissertations

Identyfikator zasobu:

oai:rcin.org.pl:110938

Źródło:

IMDiK PAN, sygn. ZS401 ; kliknij tutaj, żeby przejść

Język:

pol

Język streszczenia:

eng

Prawa:

Creative Commons Attribution BY 4.0 license

Zasady wykorzystania:

Copyright-protected material. [CC BY 4.0] May be used within the scope specified in Creative Commons Attribution BY 4.0 license, full text available at: ; -

Digitalizacja:

Mossakowski Medical Research Institute PAS

Lokalizacja oryginału:

Library of the Mossakowski Medical Research Institute PAS

Dofinansowane ze środków:

Operational Program Digital Poland, 2014-2020, Measure 2.3: Digital accessibility and usefulness of public sector information; funds from the European Regional Development Fund and national co-financing from the state budget.

Dostęp:

Open