Overview

The mammalian brain is characterized by the richest collection of cell types amongst vertebrate tissues. Fundamental players in this tremendous complexity are neural progenitors that during development serve as the ultimate origin of all three major neural cell types composing the mature brain. During development, neural progenitors are specified to a vast array of subtypes at topologically well-defined locations and precise developmental stages. This highly coordinated cell genesis represents a crucial step in the assemblage and consequent functions of the complex neural circuitry. The central goal of our laboratory is to decipher the molecular and cellular codes underlying the neural specification and neuronal differentiation programmes during neural development and understand how the same programmes are impaired in brain diseases. This knowledge is pivotal to cell replacement approaches to the damaged brain and to the generation of cellular models of brain diseases mandatory for disclosing the molecular bases of diseases and for establishing effective drug discovery programmes. Neural connections

Research directions

Research activity in the lab is directed toward the understanding of mechanisms by which neuronal diversity is established during the development and maturation of the Central Nervous System. The final aim is to exploit this knowledge to develop molecular and cellular tools for prospect cellular and pharmacological therapeutic interventions to the diseased brain. We pursue these goals by using both mammalian neural tissues and neuralizing processes applied to pluripotent stem cell (PSC) systems. We routinely combine a variety of techniques and tools to conduct our research including human PSC-derived 2D and 3D neural cultures, molecular biology, biochemistry and cell-based assays.

There are currently three major areas of interest in the lab:

  • Developing protocols for achieving the generation of defined subtypes of functional mature neurons, astrocytes and oligodendrocytes from human PSCs.
  • Decoding of the cellular and molecular mechanisms of human CNS development, with particular focus on cortical neuronal cell types.
  • Modelling human brain disorders with iPSCs to understand the molecular mechanisms of diseases, disclose pathological-relevant phenotypes and develop drug screening platforms. Our aim is to model human brain diseases by reprogramming patient-derived somatic cells with neurodevelopmental and neuropsychiatric diseases. The iPSC lines are subjected to differentiation into patient-specific neural cell types and disease-relevant neurons and are interrogated to disclose the molecular mechanisms causing the onset and/or driving the disease progression. To this end, assays monitoring self-renewal and differentiation potential, as well as the function of neuronal subtypes are used.

Group members

  • Luciano Conti, PI
  • Alessandro Cutarelli, Postdoc
  • Elena Vecchi, Visiting Postdoc
  • Ingrid Battistella, PhD Student
  • Giulia Fioravanti, PhD Student
  • Master and Bachelor Students

Ongoing collaborations

  • Marco Onorati, Dept. Biology, University of Pisa, Pisa - ITALY
  • Elisa Giorgio, Dept. Molecular Medicine, University of Pavia, Pavia - ITALY
  • Giorgio Merlo, Molecular Biotechnology Center, University of Torino, Turin - ITALY
  • Carlo Sala, CNR Neuroscience Institute, Monza - ITALY
  • Armando D’Agostino, Dept. Health Sciences, University of Milano, Milan - ITALY
  • Corrado Corti, EURAC Institute for Biomedicine, Bolzano - ITALY
  • Carlo Musio, CNR IBF, Trento - ITALY
  • Stefano Biressi, Dept. CIBIO, Università di Trento, Trento - ITALY
  • Ada Maria Tata, Dept. Biology and Biotechnology, Sapienza University of Rome, Rome - ITALY
  • Yvan Torrente, Dept. Neurological Sciences, University of Milano, Milan - Italy
  • Noel Buckley, Dept. Psychiatry, University of Oxford, Oxford - UK
  • Steve Pollard, Centre of Regenerative Medicine, University of Edinburgh - UK
  • Frank Edenhofer, Institute of Molecular Biology, University of Innsbruck, Innsbruck - AUSTRIA

Selected publications

Last three years pubblications (for a complete list see https://orcid.org/0000-0002-2050-9846).

Gilmozzi, V., Gentile, G., Riekschnitz, D.A., Von Troyer, M., Lavdas, A.A., Kerschbamer, E., Weichenberger, C.X., Rosato Siri, M.D., Casarosa, S., Conti L., Pramstaller, P.P., Hicks, A.A., Pichler, I., and Zanon, A. Generation of hiPSC-derived functional dopaminergic neurons in alginate-based 3D culture (2021). Frontiers in Cell and Developmental Biology 9, 708389.

Cutarelli, A., Martínez-Rojas, V.A., Tata, A., Battistella, I., Rossi, D., Arosio, D., Musio, C., and Conti L. A Monolayer System for the Efficient Generation of Motor Neuron Progenitors and Functional Motor Neurons from Human Pluripotent Stem Cells (2021). Cells 10, 1127.

Pollini, D., Loffredo, R., Rossi, A., Micaelli, M., Cardano, M., Bonomo, I., Licata, N.V., Peroni, D., Crippa, V., Dessi, E., Quattrone, A., Poletti, A., Conti L., and Provenzani, A. MATR3-dependent multilayer regulation of OCT4, NANOG and LIN28A is essential for the maintenance of the human pluripotency (2021). iScience 24(3):102197.

Dell' Amico, C., Tata, A., Pellegrino, E., Onorati, M., and Conti L. Genome editing in stem cells for genetic neurodisorders (2021). Prog Mol Biol Transl Sci. 2021;182:403-438.

Pistello, M., Dell’Anno, M.T., Baggiani, M., Conti L., and Onorati., M. Human Neural Stem Cell Systems to Explore Pathogen-Related Neurodevelopmental and Neurodegenerative Disorders (2020). Cells. 9(8):E1893.

Toparlak, Ö.D., Zasso, J., Bridi, S., Dalla Serra, M., Macchi, P., Conti L., Baudet, M.L., and Mansy, S.S. Artificial cells drive neural differentiation (2020). Science Advances. 6(38):eabb4920.

Marcatili, M., Sala, C., Dakanalis, A., Colmegna, F., D’Agostino, A., Gambini, O., Dell’Osso, B., Benatti, B., Conti L. and Clerici, M. Human Induced pluripotent stem cells technology in Treatment Resistant Depression: novel strategies and opportunities to unravel ketamine’s fast-acting antidepressant mechanisms (2020). Ther Adv Psychopharmacol.;10:2045125320968331.

Cristofaro, I., Alessandrini, F., Spinello, Z., Fiore, M., Dini, L., Conti L. and Tata, A.M. Cross Interaction between M2 Muscarinic Receptor and Notch1/EGFR Pathway in Human Glioblastoma Cancer Stem Cells: Effects on Cell Cycle Progression and Survival (2020). Cells 9(3). pii: E657.

Cristofaro, I., Limongi, C., Piscopo, P., Crestini, A., Fiore, M., Dini, L., Conti L., Confaloni, A. and Tata, A.M. M2 receptor activation counteracts the Glioblastoma Cancer Stem Cell response to hypoxia condition (2020). Int. J. Mol. Sci. 2020, 21, 1700.

Cutarelli, A., Ghio, S., Zasso, J., Speccher, A., Scarduelli, G., Roccuzzo, M., Crivellari, M., Pugno, M.N., Casarosa, S., Boscardin, M., Conti L. Vertically-Aligned Functionalized Silicon Micropillars for 3D Culture of Human Pluripotent Stem Cell-Derived Cortical Progenitors (2019). Cells 9(1). pii: E88.

Frisina, F., Valetti, G., Zuccarini, G., Conti L., Merlo, G.R. Advances in the use of GABAergic interneurons for the treatment of epilepsy (2019). J Stem Cell Ther Transplant.; 3: 009-022.

Giorgio, E., Lorenzati, M., Rivetti di Val Cervo, P., Brussino, A., Cernigoj, M., Della Sala, E., Bartoletti Stella, A., Ferrero, M., Capellari, S., Cortelli, P., Conti L., Cattaneo, E., Buffo, A., Brusco, A. Allele-specific silencing by siRNA can finely modulate gene expression for therapy of disorders due to gene duplication: a proof-of-principle in Autosomal Dominant LeukoDystrophy (ADLD) (2019). Brain. 142(7):1905-1920.

Cardano, M., Zasso, J., Ruggiero, L., Di Giacomo, G., Marcatili, M., Cremona, O., Conti L.§ Epsins regulate mouse Embryonic Stem cells exit from pluripotency and neural commitment by controlling Notch activation (2019). Stem Cells International. vol. 2019, ID 4084351, 1-13.

Grassi, E., Santoro, R., Umbach, A., Grosso, A., Oliviero, S., Neri, F., Conti L., Ala, U., Provero, P., DiCunto, F., Merlo, G.R. Choice of alternative polyadenylation sites, mediated by the RNA-binding protein Elavl3, plays a role in differentiation of Inhibitory neuronal progenitors (2019). Frontiers in Cellular Neuroscience 10; 12:518.