GROUP LEADER: Maria Pia Cosma (ICREA Research Professor)

POSTDOCTORAL FELLOWS: Karthik Arumugam, Marie Victoria Negeumbor, Chiara Vicario, Shoma Nakagawa, Ximena Garate

PhD STUDENTS: Martina Pesaresi, Alvaro Castells , Paola Andrea Cortes , Sergi Angel Bonilla Pons, Ruben Sebastian Perez, Pablo Gomez Garcia, Xiaochuan Tu, Jose Angel Martinez Sarmiento, Ivan Milenkovic

MASTER STUDENTS: Laura Martin

TECHNICIANS: Umberto di Vicino, Marc Alcoverro Bertran

SUMMARY

The main interest of our laboratory is to dissect mechanisms and factors controlling somatic cell reprogramming and tissue regeneration in mammalians. We showed that activation of the Wnt/ß-catenin signalling pathway enhances reprogramming of somatic cells after their fusion with embryonic stem cells. We have now identified gene networks and reprogramming factors controlled by the activation of Wnt/ß-catenin pathway. Furthermore, by using super resolution microscopy we are investigating on the remodelling of the chromatin fiber during the reprograming process. Remarkably, the activation of Wnt pathway controls regeneration in response to damage in lower and higher vertebrates. Our goal is to determine whether activation of Wnt/ß-catenin signalling controls cell-fusion-mediated regeneration in mammals. We recently showed that in vivo reprogramming of neurons and hepatocytes after fusion with hematopoietic stem and progenitor cells is a mechanism for tissue regeneration.

Cell fusion-mediated regeneration occurs in multiple tissues. BMDCs (in red) have been reported to fuse with several somatic cell types (in blue), generating hybrid cells that contain both parental DNA. Such events were seen in multiple tissues, including skeletal muscle, liver, lungs, intestine, skin, heart, brain and the retina. Pesaresi et al. FEBS Journal 2018.

Fig. 1

Cell fusion-mediated regeneration occurs in multiple tissues. BMDCs (in red) have been reported to fuse with several somatic cell types (in blue), generating hybrid cells that contain both parental DNA. Such events were seen in multiple tissues, including skeletal muscle, liver, lungs, intestine, skin, heart, brain and the retina. Pesaresi et al. FEBS Journal 2018.

To burst endogenous repair in the retina. After damage bone marrow cells migrate in the retina of mice, can fuse with Muller glia cells and the hybrids differentiate in ganglion cell neurons (Pesaresi et al eBiomedicine 2018).

Fig. 2

To burst endogenous repair in the retina. After damage bone marrow cells migrate in the retina of mice, can fuse with Muller glia cells and the hybrids differentiate in ganglion cell neurons (Pesaresi et al eBiomedicine 2018).

RESEARCH PROJECTS

  • Dissecting out how Wnt signalling controls somatic cell reprogramming.
  • Identification of novel Master Regulators controlling stem cell self-renewal and somatic cell reprogramming
  • Decoding chromatin and DNA structure in cells undergoing reprogramming and differentiation, using super-resolution microscopy.
  • Cell-fusion-mediated somatic cell reprogramming controlled by Wnt activity as a mechanism of neuron regeneration.

SELECTED PUBLICATIONS

Pesaresi, M, Bonilla S, Simonte G, Sanges D, Di Vicino U, and Cosma MP.
“Endogenous mobilization of bone-marrow cells into murine retina induces fusion mediated reprogramming of Müller glia cells.”
eBioMedicine, 30:38–51, 2018.

Pesaresi M, Bonilla-Pons S, and Cosma MP.
“In vivo somatic cell reprogramming for tissue regeneration: the emerging role of the local microenvironment.”
Current Opinion in Cell Biology, 55:119–128, 2018.

Pesaresi M, Sebastian-Perez R, and Cosma MP.
“Dedifferentiation, transdifferentiation and cell fusion: in vivo reprogramming strategies for regenerative medicine.”
FEBS Journal, Aug 13, 2018. [Epub ahead of print]