Frontiers in Molecular Neuroscience (Sep 2018)
Transdifferentiation of Human Circulating Monocytes Into Neuronal-Like Cells in 20 Days and Without Reprograming
- Alfredo Bellon,
- Alfredo Bellon,
- Alfredo Bellon,
- Alfredo Bellon,
- Alfredo Bellon,
- Alfredo Bellon,
- Alfredo Bellon,
- Amelie Wegener,
- Amelie Wegener,
- Amelie Wegener,
- Amelie Wegener,
- Adam R. Lescallette,
- Michael Valente,
- Michael Valente,
- Michael Valente,
- Seung-Kwon Yang,
- Seung-Kwon Yang,
- Robert Gardette,
- Robert Gardette,
- Julien Matricon,
- Julien Matricon,
- Faycal Mouaffak,
- Faycal Mouaffak,
- Faycal Mouaffak,
- Paula Watts,
- Lene Vimeux,
- Lene Vimeux,
- Lene Vimeux,
- Jong K. Yun,
- Yuka Imamura Kawasawa,
- Yuka Imamura Kawasawa,
- Gary A. Clawson,
- Elisabeta Blandin,
- Elisabeta Blandin,
- Boris Chaumette,
- Boris Chaumette,
- Boris Chaumette,
- Boris Chaumette,
- Therese M. Jay,
- Therese M. Jay,
- Marie-Odile Krebs,
- Marie-Odile Krebs,
- Marie-Odile Krebs,
- Vincent Feuillet,
- Vincent Feuillet,
- Vincent Feuillet,
- Anne Hosmalin,
- Anne Hosmalin,
- Anne Hosmalin
Affiliations
- Alfredo Bellon
- Penn State Hershey Medical Center, Department of Psychiatry, Hershey, PA, United States
- Alfredo Bellon
- Penn State Hershey Medical Center, Department of Pharmacology, Hershey, PA, United States
- Alfredo Bellon
- INSERM U1016, Institut Cochin, Paris, France
- Alfredo Bellon
- CNRS UMR8104, Paris, France
- Alfredo Bellon
- Université Paris Descartes, Sorbonne Paris Cite, Paris, France
- Alfredo Bellon
- INSERM UMR894, Center for Psychiatry and Neurosciences, Paris, France
- Alfredo Bellon
- Centre Hospitalier Sainte-Anne, Faculté de Médecine Paris Descartes, Service Hospitalo-Universitaire-S14, Paris, France
- Amelie Wegener
- INSERM U1016, Institut Cochin, Paris, France
- Amelie Wegener
- CNRS UMR8104, Paris, France
- Amelie Wegener
- Université Paris Descartes, Sorbonne Paris Cite, Paris, France
- Amelie Wegener
- INSERM UMR894, Center for Psychiatry and Neurosciences, Paris, France
- Adam R. Lescallette
- Penn State Hershey Medical Center, Department of Psychiatry, Hershey, PA, United States
- Michael Valente
- INSERM U1016, Institut Cochin, Paris, France
- Michael Valente
- CNRS UMR8104, Paris, France
- Michael Valente
- Université Paris Descartes, Sorbonne Paris Cite, Paris, France
- Seung-Kwon Yang
- Université Paris Descartes, Sorbonne Paris Cite, Paris, France
- Seung-Kwon Yang
- INSERM UMR894, Center for Psychiatry and Neurosciences, Paris, France
- Robert Gardette
- Université Paris Descartes, Sorbonne Paris Cite, Paris, France
- Robert Gardette
- INSERM UMR894, Center for Psychiatry and Neurosciences, Paris, France
- Julien Matricon
- Université Paris Descartes, Sorbonne Paris Cite, Paris, France
- Julien Matricon
- INSERM UMR894, Center for Psychiatry and Neurosciences, Paris, France
- Faycal Mouaffak
- Université Paris Descartes, Sorbonne Paris Cite, Paris, France
- Faycal Mouaffak
- INSERM UMR894, Center for Psychiatry and Neurosciences, Paris, France
- Faycal Mouaffak
- Centre Hospitalier Sainte-Anne, Faculté de Médecine Paris Descartes, Service Hospitalo-Universitaire-S14, Paris, France
- Paula Watts
- Sky Ridge Medical Center, Department of Internal Medicine, Lone Tree, CO, United States
- Lene Vimeux
- INSERM U1016, Institut Cochin, Paris, France
- Lene Vimeux
- CNRS UMR8104, Paris, France
- Lene Vimeux
- Université Paris Descartes, Sorbonne Paris Cite, Paris, France
- Jong K. Yun
- Penn State Hershey Medical Center, Department of Pharmacology, Hershey, PA, United States
- Yuka Imamura Kawasawa
- Penn State Hershey Medical Center, Department of Pharmacology, Hershey, PA, United States
- Yuka Imamura Kawasawa
- Penn State Hershey Medical Center, Department of Biochemistry and Molecular Biology, Institute for Personalized Medicine, Hershey, PA, United States
- Gary A. Clawson
- 0Gittlen Cancer Research Laboratories, Department of Pathology, Penn State University College of Medicine, Hershey, PA, United States
- Elisabeta Blandin
- Penn State Hershey Medical Center, Department of Psychiatry, Hershey, PA, United States
- Elisabeta Blandin
- 1Penn State Hershey Medical Center, Neural & Behavioral Sciences, Hershey, PA, United States
- Boris Chaumette
- Université Paris Descartes, Sorbonne Paris Cite, Paris, France
- Boris Chaumette
- INSERM UMR894, Center for Psychiatry and Neurosciences, Paris, France
- Boris Chaumette
- Centre Hospitalier Sainte-Anne, Faculté de Médecine Paris Descartes, Service Hospitalo-Universitaire-S14, Paris, France
- Boris Chaumette
- 2Montreal Neurological Institute and Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada
- Therese M. Jay
- Université Paris Descartes, Sorbonne Paris Cite, Paris, France
- Therese M. Jay
- INSERM UMR894, Center for Psychiatry and Neurosciences, Paris, France
- Marie-Odile Krebs
- Université Paris Descartes, Sorbonne Paris Cite, Paris, France
- Marie-Odile Krebs
- INSERM UMR894, Center for Psychiatry and Neurosciences, Paris, France
- Marie-Odile Krebs
- Centre Hospitalier Sainte-Anne, Faculté de Médecine Paris Descartes, Service Hospitalo-Universitaire-S14, Paris, France
- Vincent Feuillet
- INSERM U1016, Institut Cochin, Paris, France
- Vincent Feuillet
- CNRS UMR8104, Paris, France
- Vincent Feuillet
- Université Paris Descartes, Sorbonne Paris Cite, Paris, France
- Anne Hosmalin
- INSERM U1016, Institut Cochin, Paris, France
- Anne Hosmalin
- CNRS UMR8104, Paris, France
- Anne Hosmalin
- Université Paris Descartes, Sorbonne Paris Cite, Paris, France
- DOI
- https://doi.org/10.3389/fnmol.2018.00323
- Journal volume & issue
-
Vol. 11
Abstract
Despite progress, our understanding of psychiatric and neurological illnesses remains poor, at least in part due to the inability to access neurons directly from patients. Currently, there are in vitro models available but significant work remains, including the search for a less invasive, inexpensive and rapid method to obtain neuronal-like cells with the capacity to deliver reproducible results. Here, we present a new protocol to transdifferentiate human circulating monocytes into neuronal-like cells in 20 days and without the need for viral insertion or reprograming. We have thoroughly characterized these monocyte-derived-neuronal-like cells (MDNCs) through various approaches including immunofluorescence (IF), flow cytometry, qRT-PCR, single cell mRNA sequencing, electrophysiology and pharmacological techniques. These MDNCs resembled human neurons early in development, expressed a variety of neuroprogenitor and neuronal genes as well as several neuroprogenitor and neuronal proteins and also presented electrical activity. In addition, when these neuronal-like cells were exposed to either dopamine or colchicine, they responded similarly to neurons by retracting their neuronal arborizations. More importantly, MDNCs exhibited reproducible differentiation rates, arborizations and expression of dopamine 1 receptors (DR1) on separate sequential samples from the same individual. Differentiation efficiency measured by cell morphology was on average 11.9 ± 1.4% (mean, SEM, n = 38,819 cells from 15 donors). To provide context and help researchers decide which in vitro model of neuronal development is best suited to address their scientific question,we compared our results with those of other in vitro models currently available and exposed advantages and disadvantages of each paradigm.
Keywords