PhD Discussions Sessions: Lorena de Oñate & Anita Kosmalska

Research on cardiac differentiation from pluripotent stem cells: how to get beating cells in a dish

Probably, the gain in organ complexity and cell function has led to a decrease in healing capacities in the adult mammalian heart. In an effort to generate new venues for the generation of functional cardiac cells we have explored the possibility to manipulate cell fate and plasticity making use of different cellular systems. First, taking advantage of pluripotent stem cells we have defined chemically based protocols in order to generate cardiac cells from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSC). Second, by a cell conversion approach, we have been able to produce cardiomyocyte-like cells from human fibroblasts by overexpression of specific lineage transcription factors. In parallel, to overcome several drawbacks related to both processes (i.e: purity of final cell populations), we have efficiently developed a reporter cell line for the cardiac gene alpha Myosin Heavy Chain (MYH6) by both TALEN and CRISPR/CAS9 genome editing approaches that will help us to define accurate protocols for cardiac differentiation, and more importantly, to underscore the molecular and cellular events driving human cardiomyocyte differentiation.

Physical principles of membrane remodelling during cell mechanoadaptation

Biological processes in any physiological environment involve changes in cell shape, which must be accommodated by their physical envelope – the bilayer membrane. However, the fundamental biophysical principles by which the cell membrane allows for and responds to shape changes remain unclear. Here we show that the 3D remodelling of the membrane in response to a broad diversity of physiological perturbations can be explained by a purely mechanical process. This process is passive, local, almost instantaneous, prior to any active remodelling, and generates different types of membrane invaginations that can repeatedly store and release large fractions of the cell membrane. We further demonstrate that the shape of those invaginations is determined by the minimum elastic and adhesive energy required to store both membrane area and liquid volume at the cell-substrate interface. Once formed, cells reabsorb the invaginations through an active process with duration of the order of minutes.

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