Transdifferentiation of Human Circulating Monocytes Into Neuronal-Like Cells in 20 Days and Without Reprograming
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, inexpensi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2018.00323/full |
| _version_ | 1828307657525559296 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Alfredo Bellon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T15:00:59Z |
| format | Article |
| id | doaj.art-38455e49d6fc4294acadec196640761d |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-13T15:00:59Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-38455e49d6fc4294acadec196640761d2022-12-22T02:42:18ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-09-011110.3389/fnmol.2018.00323382330Transdifferentiation of Human Circulating Monocytes Into Neuronal-Like Cells in 20 Days and Without ReprogramingAlfredo Bellon0Alfredo Bellon1Alfredo Bellon2Alfredo Bellon3Alfredo Bellon4Alfredo Bellon5Alfredo Bellon6Amelie Wegener7Amelie Wegener8Amelie Wegener9Amelie Wegener10Adam R. Lescallette11Michael Valente12Michael Valente13Michael Valente14Seung-Kwon Yang15Seung-Kwon Yang16Robert Gardette17Robert Gardette18Julien Matricon19Julien Matricon20Faycal Mouaffak21Faycal Mouaffak22Faycal Mouaffak23Paula Watts24Lene Vimeux25Lene Vimeux26Lene Vimeux27Jong K. Yun28Yuka Imamura Kawasawa29Yuka Imamura Kawasawa30Gary A. Clawson31Elisabeta Blandin32Elisabeta Blandin33Boris Chaumette34Boris Chaumette35Boris Chaumette36Boris Chaumette37Therese M. Jay38Therese M. Jay39Marie-Odile Krebs40Marie-Odile Krebs41Marie-Odile Krebs42Vincent Feuillet43Vincent Feuillet44Vincent Feuillet45Anne Hosmalin46Anne Hosmalin47Anne Hosmalin48Penn State Hershey Medical Center, Department of Psychiatry, Hershey, PA, United StatesPenn State Hershey Medical Center, Department of Pharmacology, Hershey, PA, United StatesINSERM U1016, Institut Cochin, Paris, FranceCNRS UMR8104, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cite, Paris, FranceINSERM UMR894, Center for Psychiatry and Neurosciences, Paris, FranceCentre Hospitalier Sainte-Anne, Faculté de Médecine Paris Descartes, Service Hospitalo-Universitaire-S14, Paris, FranceINSERM U1016, Institut Cochin, Paris, FranceCNRS UMR8104, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cite, Paris, FranceINSERM UMR894, Center for Psychiatry and Neurosciences, Paris, FrancePenn State Hershey Medical Center, Department of Psychiatry, Hershey, PA, United StatesINSERM U1016, Institut Cochin, Paris, FranceCNRS UMR8104, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cite, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cite, Paris, FranceINSERM UMR894, Center for Psychiatry and Neurosciences, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cite, Paris, FranceINSERM UMR894, Center for Psychiatry and Neurosciences, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cite, Paris, FranceINSERM UMR894, Center for Psychiatry and Neurosciences, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cite, Paris, FranceINSERM UMR894, Center for Psychiatry and Neurosciences, Paris, FranceCentre Hospitalier Sainte-Anne, Faculté de Médecine Paris Descartes, Service Hospitalo-Universitaire-S14, Paris, FranceSky Ridge Medical Center, Department of Internal Medicine, Lone Tree, CO, United StatesINSERM U1016, Institut Cochin, Paris, FranceCNRS UMR8104, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cite, Paris, FrancePenn State Hershey Medical Center, Department of Pharmacology, Hershey, PA, United StatesPenn State Hershey Medical Center, Department of Pharmacology, Hershey, PA, United StatesPenn State Hershey Medical Center, Department of Biochemistry and Molecular Biology, Institute for Personalized Medicine, Hershey, PA, United States0Gittlen Cancer Research Laboratories, Department of Pathology, Penn State University College of Medicine, Hershey, PA, United StatesPenn State Hershey Medical Center, Department of Psychiatry, Hershey, PA, United States1Penn State Hershey Medical Center, Neural & Behavioral Sciences, Hershey, PA, United StatesUniversité Paris Descartes, Sorbonne Paris Cite, Paris, FranceINSERM UMR894, Center for Psychiatry and Neurosciences, Paris, FranceCentre Hospitalier Sainte-Anne, Faculté de Médecine Paris Descartes, Service Hospitalo-Universitaire-S14, Paris, France2Montreal Neurological Institute and Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, QC, CanadaUniversité Paris Descartes, Sorbonne Paris Cite, Paris, FranceINSERM UMR894, Center for Psychiatry and Neurosciences, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cite, Paris, FranceINSERM UMR894, Center for Psychiatry and Neurosciences, Paris, FranceCentre Hospitalier Sainte-Anne, Faculté de Médecine Paris Descartes, Service Hospitalo-Universitaire-S14, Paris, FranceINSERM U1016, Institut Cochin, Paris, FranceCNRS UMR8104, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cite, Paris, FranceINSERM U1016, Institut Cochin, Paris, FranceCNRS UMR8104, Paris, FranceUniversité Paris Descartes, Sorbonne Paris Cite, Paris, FranceDespite 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.https://www.frontiersin.org/article/10.3389/fnmol.2018.00323/fullstem cellsdopamineschizophrenianeuritein vitro modelGABA |
| spellingShingle | 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 Transdifferentiation of Human Circulating Monocytes Into Neuronal-Like Cells in 20 Days and Without Reprograming Frontiers in Molecular Neuroscience stem cells dopamine schizophrenia neurite in vitro model GABA |
| title | Transdifferentiation of Human Circulating Monocytes Into Neuronal-Like Cells in 20 Days and Without Reprograming |
| title_full | Transdifferentiation of Human Circulating Monocytes Into Neuronal-Like Cells in 20 Days and Without Reprograming |
| title_fullStr | Transdifferentiation of Human Circulating Monocytes Into Neuronal-Like Cells in 20 Days and Without Reprograming |
| title_full_unstemmed | Transdifferentiation of Human Circulating Monocytes Into Neuronal-Like Cells in 20 Days and Without Reprograming |
| title_short | Transdifferentiation of Human Circulating Monocytes Into Neuronal-Like Cells in 20 Days and Without Reprograming |
| title_sort | transdifferentiation of human circulating monocytes into neuronal like cells in 20 days and without reprograming |
| topic | stem cells dopamine schizophrenia neurite in vitro model GABA |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2018.00323/full |
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