ESR7

Dynamic changes in transcription and epigenetic profile of fibro-adipogenic progenitors (FAPs) in healthy and dystrophic muscles, and modulation by epigenetic drugs (HDACi).

Emilia Skafida
Emilia SkafidaFondazione Santa Lucia

I received my BSc and MSc degrees from University of Crete in Greece, where I specialized in Molecular Biology and Biomedicine.

During my studies, I have developed a great interest for developmental biology which has leaded me to explore different flavours of this field; from hematopoietic stem cell differentiation in my BSc thesis and embryonic stem cell studies during my Erasmus internship in Milan to Drosophila gut development in my MSc thesis.

My latest project as a short-term Marie Curie fellow of the EvoCELL network in France was about regeneration studies in a crustacean species, Parhyale hawaiensis.  There I got attracted by Regenerative Biology, a fact that leaded me to be part in RENOIR network.

During my PhD project I will study the dynamic changes in transcription and epigenetic profile of fibro-adipogenic progenitors in healthy and dystrophic muscles, aiming to elucidate their response to treatment with epigenetic drugs.

Fondazione Santa Lucia

Fondazione Santa Lucia

Italy

Partner Profile

Topic

Muscle homeostasis relies on a population of muscle stem cells, the satellite cells (SCs), which support post-natal growth and are mainly responsible for skeletal muscle repair. It is well known that in addition to the canonical muscle stem cells, different cell types can in part influence either negatively or positively skeletal muscle homeostasis, including the macrophages, the resident fibro/adipogenic progenitors (FAPs) expressing platelet-derived growth-factor receptor (PDGFR)-α and the PW1/Peg3 positive interstitial cells (myoPiCS).

We will focus on the non-satellite cell progenitors myoPICs, which display pronounced myogenic potential but cannot compensate for the lack of SCs. To further characterize these cells and discriminate myoPICs from other sub-populations, including PW1+/PDGFRα+ FAPs, ESR7 will use single cell transcriptomic analysis of FAPs isolated from WT and mdx mice (model of human DMD) as well as from DMD patients, exposed or not to HDACi, to isolate potential subpopulations of FAPs and define their gene expression profiles.

Objectives
  • To characterise the transcriptome profiling and the epigenetic landscape in FAPs isolated from mdx mice, at different stages of disease progression and in response to treatment with HDAC inhibitors – a pharmacological intervention currently in clinical trial with DMD boys

  • To identify distinct subpopulations of FAPs in muscles of mdx mice at different stages of disease progression and in response to treatment with HDAC inhibitors
  • To validate data generated in points 1 and 2 in FAPs isolated from muscles of DMD patients

PHD Program

Ph.D. Programme in Translational and Molecular Medicine (DIMET),

University of Milano Bicocca.

Supervisor

Lucia Latella

Fondazione Santa Lucia, Epigenetics and Regenerative Pharmacology Lab

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