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- W2286161981 abstract "In this thesis, we investigated the two fundamental characteristics of human embryonic stem cells (hESCs), being their pluripotency and differentiation potential. Firstly, we have shown that hESC derivation in the presence of Activin A (ActA) predisposes these ActA-derived hESC lines towards a primordial germ cell (PGC) fate unlike the hESCs derived in standard culture conditions. The undifferentiated ActA-derived hESC lines demonstrated an inherent increased expression of early PGC markers STELLA and cKIT. Following their differentiation for seven days in the presence of bone morphogenic protein 4 (BMP4), widely known to induce germ cell differentiation, the pre-meiotic marker VASA was significantly upregulated both at the transcript and protein level in comparison to the differentiated hESC lines derived in standard culture conditions. We also observed an active TGFβ/Activin signalling during the differentiation process as proven by the nuclear translocation of SMAD2/3 following phosphorylation. Next, we further investigated the role of ActA in inducing in vitro PGC fate upon its exogenous supplementation during hESC differentiation. Differentiation of ActAderived and standard hESC lines in the presence of both ActA and BMP4 significantly improved PGC gene expression compared to BMP4 alone. We also demonstrated the need to mimic in vivo environment for differentiation purposes as exposure of these seven-day old in vitro-derived PGCs to reproductive hormones resulted in the generation of pre-meiotic germ cells. Additionally, we suggest a synergistic developmental relationship between the endodermal and PGC lineages during in vitro differentiation of hESCs, which has not been reported earlier. As the biggest success in mouse for in vitro germ cell formation from stem cells was achieved when starting from naive pluripotent stem cells, we attempted to convert existing primed hESCs into their naive state. We were able to generate naive hESCs using a novel naive pluripotency inducing media, which also allowed the derivation of naive mESCs. Hence, we suggest that alternative routes exist to induce naive pluripotency in human." @default.
- W2286161981 created "2016-06-24" @default.
- W2286161981 creator A5028495941 @default.
- W2286161981 date "2015-01-01" @default.
- W2286161981 modified "2023-09-28" @default.
- W2286161981 title "Human embryonic stem cells : different shades of pluripotency and differentiation potential" @default.
- W2286161981 hasPublicationYear "2015" @default.
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