Reprogramming and Regeneration

GENE REGULATION, STEM CELLS AND CANCER

GROUP LEADER:
Maria Pia Cosma (ICREA Research Professor)

POSTDOCTORAL FELLOWS:
Karthik Arumugam, Marie Victoria Negeumbor, Chiara Vicario, Anna Oddone , Joao Frade, Shoma Nakagawa

PhD STUDENTS:
Martina Pesaresi, Alvaro Castells, Paola Andrea Cortes, Sergi Angel Bonilla Pons, Elena Tantardini, Ruben Sebastian Perez, Pablo Gomez Garcia

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 fibre 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.

Fig. 01

PoSTAC is a gene visualisation tool that combines CRISPR/dCas9 with SunTag labelling and polycistronic vectors. PoSTAC enables live cell and super-resolution imaging of multiple genes with high spatiotemporal resolution and high sensitivity (Neguembor et al. NAR 2017)

Fig. 2

After liver hepatectomy bone marrow cells migrate in the resected liver and fuse with the hepatocytes. The resulting hybrids are essential for liver regeneration (Pedone et al Cell Reports 2017).

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

Neguembor MV, Sebastian-Perez R, Aulicino F, Gomez-Garcia PA, *Cosma MP, and *Lakadamyali M.
“PoSTAC (Polycistronic SunTAg modified CRISPR) enables live-cell and super resolution visualization of multiple genes.”
Nucleic Acids Res, *co-last authors (2017).

Theka I, Sottile F, Aulicino F, Castells Garcia A and Cosma MP.
“Reduced expression of Paternally Expressed Gene-3 enhances somatic cell reprogramming through mitochondrial activity perturbation.”
Scientific Reports, (2017).

Ricci MA, *Cosma MP and *Lakadamyali M.
“Super Resolution imaging of chromatin in pluripotency, differentiation, and reprogramming.”
Current Opinion in Genetics and Development, *co-last authors (2017).

De Jaime-Soguero A, Aulicino F, Ertaylan G, Grieco A, Cerrato A, Tallam A, del Sol A, *Cosma MP and *Lluis F.
“Wnt/b-catenin/Tcf1 pathway controls mouse embryonic stem cell cycle progression and proliferation by regulating the Ink4/Arf locus.”
Plos Genetics, *co-last authors (2017).

Pedone E, Oltenau VA, Marucci L, Muñoz-Martin MI, Youssef SA, de Bruin A, and Cosma MP.
“Modelling Dynamics and Function of Bone Marrow Cells in Mouse Liver Regeneration.”
Cell Reports, 18:107–121 (2017).