Oct 24, 2016
from 04:00 PM to 05:00 PM
|Where||Genetics Part II Room|
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Gabriella Minchiotti (IGB Naples) will give a seminar in the partII class of the Department of Genetics, on 24th of October at 16:00 on :
Extrinsic control of embryonic stem cell plasticity: learning from development and beyond
Institute of Genetics and Biophysics "A. Buzzati-Traverso", CNR, Naples.
Embryonic stem cell (ESC) plasticity arises from their ability to dynamically interconvert between different states of pluripotency. These reversible/metastable states are characterized by distinct transcriptome and epigenetic patterns, and are shifting our perception of stem cells from being a functionally uniform to a dynamic pool of alternating cell subsets. Known molecular determinants of such plasticity are mainly transcription factors, whereas the extrinsic regulation and the metabolic control of this process have been largely unexplored. We have contributed to this field using different strategies based on development-inspired cues and unbiased high-throughput phenotypic screenings. We have recently demonstrated that ESC phenotypic and molecular identity is established and maintained through a nutrient stress condition generated by an intrinsic starvation of the nonessential amino acid L-Proline (L-Pro), which is under the control of the amino acid stress response (AAR)/Atf4 pathway. We will discuss recent findings from our laboratory on the key role of L-Pro metabolism in the control of mouse ESC identity and on how the relative levels of two physiological metabolites, namely L-Pro and Ascorbic acid (Vitamin C), impact on the epigenetic, metabolic and transcriptional status of ESCs capturing different states in the pluripotency continuum.