Epigenetic regulation of skeletal muscle FAPs identity

(This conference will take place in English.)

Joana Esteves de Lima
Researcher
Université Paris Est Créteil
Institut National de la Santé et de la Recherche Médicale (INSERM)
Mondor Institute for Biomedical Research (IMRB)
F-94010 Créteil, France

This conference is hosted by Jean-François Côté and will be held in person in the IRCM Jacques-Genest Auditorium.

About this conference

Chromatin architecture impacts gene expression and defines cell lineage specification. The role of the histone variant H3.3 and its chaperone HIRA, in the gene regulation of somatic cell lineage progression remains under investigated. We recently showed that satellite cells lacking HIRA lose myogenic cell identity and fail to repair the muscle. Since HIRA is a ubiquitous protein, we aimed to assess whether the HIRA-H3.3 axis is required to sustain the cell identity of other lineages. By combining tissue-specific and inducible mouse lines, we addressed the consequences of HIRA loss in fibro-adipogenic progenitors (FAPs) in skeletal muscle tissue upon injury. We found that FAP numbers are reduced in the absence of HIRA, which leads to a delayed regeneration. Additionally, HIRA-depleted FAPs exhibit reduced proliferative capacity and increased cell death. These cells further present increased fibrogenic potential, leading to higher fibrotic deposition. In addition to intrinsic defects, FAPs lacking HIRA display a disruptive crosstalk between neighboring cells, with satellite cell and macrophage numbers being affected. Moreover, we identified a switch in the metabolic profile of HIRA-depleted FAPs that we hypothesize is linked to the increased expression of fibrotic genes and fibrogenic potential. To link the observed phenotype with changes in H3.3 incorporation we are performing Cut&Tag experiments. We hypothesize that HIRA-H3.3 axis is required to maintain FAPs lineage progression during muscle regeneration and that it safeguards lineage-specific gene expression and cell identity.

About Joana Esteves de Lima  

I am an academic researcher at INSERM and I work on skeletal muscle development and epigenetic regulation in the laboratory of Prof Relaix in Mondor Institut for Biomedical Research.

Throughout the years my research focus was on fundamental research with the use of skeletal muscle tissue and the myogenic programme as a model to study diverse biological questions in a variety of animal models. I addressed questions that contributed to the understanding of how signaling pathway networks, mechano-transduction signals and chromatin architecture regulate muscle stem cell maintenance in development and adult systems. I now combine my expertise in epigenetic regulation, cell differentiation and mouse molecular tools to focus on how alterations in the chromatin architecture are implicated in cell identity, both in development and adult muscle regeneration contexts.

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