Journal of Stem Cell Research & Therapy

Human amniocytes are receptive to chemical induced reprogramming to pluripotency

7^th Annual Conference on Stem Cell and Regenerative Medicine

August 04-05, 2016 Manchester, UK

Pascale V Guillot

University College London, UK

Posters & Accepted Abstracts: J Stem Cell Res Ther

Abstract:

Restoring the pluripotent state of somatic cells using chemical compounds alone would be a major step forward in developing clinical grade pluripotent stem cells but this has not yet been reported in human cells. We previously demonstrated that human amniocytes cultivated with valproic acid (VPA_AFS cells) formed well differentiated teratomas containing derivates of the three germ layers when transplanted into immunodeficient mice, indicating they acquired functional pluripotency. However, VPA_AFS cells remained distinct from hESCs, questioning the relationship between modulation of cell fate potency and molecular regulation of the pluripotency network. Here, we used single cell analysis and functional assays to analyze the features of the molecular state of VPA_AFS cells and understand how they relate to hESCs. We reveal that VPA treatment resulted in a homogenous population of self renewing non-transformed cells and induced transcriptional and phenotypical changes that fulfill hallmarks of pluripotency i.e., a short G1 phase, a dependence on glycolytic metabolism, expression of epigenetic modifications on histones 3 and 4 and reactivation of endogenous OCT4 and downstream targets (including Tra-1- 60, REX1, DNMT3B, NANOG and SOX2), which were expressed in all VPA_AFS cells but at a lower level than that observed in hESCs. Our data identify for the first time the pluripotent transcriptional signature and metabolic status of human chemically induced pluripotent stem cells.

Biography :

Email: p.guillot@ucl.ac.uk