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Your search keyword '"Schweitzer, Christophe"' showing total 13 results
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13 results on '"Schweitzer, Christophe"'

4. Alzheimer's Risk Gene TREM2 Determines Functional Properties of New Type of Human iPSC-Derived Microglia

Author

Neurociencias, Neurozientziak, Reich, Marvin, Paris Guerrero, Ignacio, Ebeling, Martin, Dahm, Nadine, Schweitzer, Christophe, Reinhardt, Dieter, Schmucki, Roland, Prasad, Megana, Kochl, Fabian, Leist, Marcel, Cowley, Sally A., Zhang, Jitao David, Patsch, Christoph, Gutbier, Simon, Britschgi, Markus, Neurociencias, Neurozientziak, Reich, Marvin, Paris Guerrero, Ignacio, Ebeling, Martin, Dahm, Nadine, Schweitzer, Christophe, Reinhardt, Dieter, Schmucki, Roland, Prasad, Megana, Kochl, Fabian, Leist, Marcel, Cowley, Sally A., Zhang, Jitao David, Patsch, Christoph, Gutbier, Simon, and Britschgi, Markus

Abstract

Microglia are key in the homeostatic well-being of the brain and microglial dysfunction has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Due to the many limitations to study microglia in situ or isolated for large scale drug discovery applications, there is a high need to develop robust and scalable human cellular models of microglia with reliable translatability to the disease. Here, we describe the generation of microglia-like cells from human induced pluripotent stem cells (iPSC) with distinct phenotypes for mechanistic studies in AD. We started out from an established differentiation protocol to generate primitive macrophage precursors mimicking the yolk sac ontogeny of microglia. Subsequently, we tested 36 differentiation conditions for the cells in monoculture where we exposed them to various combinations of media, morphogens, and extracellular matrices. The optimized protocol generated robustly ramified cells expressing key microglial markers. Bulk mRNA sequencing expression profiles revealed that compared to cells obtained in co-culture with neurons, microglia-like cells derived from a monoculture condition upregulate mRNA levels for Triggering Receptor Expressed On Myeloid Cells 2 (TREM2), which is reminiscent to the previously described disease-associated microglia. TREM2 is a risk gene for AD and an important regulator of microglia. The regulatory function of TREM2 in these cells was confirmed by comparing wild type with isogenic TREM2 knock-out iPSC microglia. The TREM2-deficient cells presented with stronger increase in free cytosolic calcium upon stimulation with ATP and ADP, as well as stronger migration towards complement C5a, compared to TREM2 expressing cells. The functional differences were associated with gene expression modulation of key regulators of microglia. In conclusion, we have established and validated a work stream to generate functional human iPSC-derived microglia-like cells by applying a directed a

Published
2021

5. Alzheimer’s Risk Gene TREM2 Determines Functional Properties of New Type of Human iPSC-Derived Microglia

Author

Reich, Marvin, primary, Paris, Iñaki, additional, Ebeling, Martin, additional, Dahm, Nadine, additional, Schweitzer, Christophe, additional, Reinhardt, Dieter, additional, Schmucki, Roland, additional, Prasad, Megana, additional, Köchl, Fabian, additional, Leist, Marcel, additional, Cowley, Sally A., additional, Zhang, Jitao David, additional, Patsch, Christoph, additional, Gutbier, Simon, additional, and Britschgi, Markus, additional

Published
2021
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6. Potent and Selective BACE-1 Peptide Inhibitors Lower Brain Aβ Levels Mediated by Brain Shuttle Transport

Author

Ruderisch, Nadine, primary, Schlatter, Daniel, additional, Kuglstatter, Andreas, additional, Guba, Wolfgang, additional, Huber, Sylwia, additional, Cusulin, Carlo, additional, Benz, Jörg, additional, Rufer, Arne Christian, additional, Hoernschemeyer, Joerg, additional, Schweitzer, Christophe, additional, Bülau, Tina, additional, Gärtner, Achim, additional, Hoffmann, Eike, additional, Niewoehner, Jens, additional, Patsch, Christoph, additional, Baumann, Karlheinz, additional, Loetscher, Hansruedi, additional, Kitas, Eric, additional, and Freskgård, Per-Ola, additional

Published
2017
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7. Cargo Delivery into the Brain by in vivo identified Transport Peptides

Author

Urich, Eduard, primary, Schmucki, Roland, additional, Ruderisch, Nadine, additional, Kitas, Eric, additional, Certa, Ulrich, additional, Jacobsen, Helmut, additional, Schweitzer, Christophe, additional, Bergadano, Alessandra, additional, Ebeling, Martin, additional, Loetscher, Hansruedi, additional, and Freskgård, Per-Ola, additional

Published
2015
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8. Comprehensive in vitro pharmacological selectivity profile of oseltamivir prodrug (Tamiflu®) and oseltamivir active metabolite

Author

Lindemann, Lothar, primary, Jacobsen, Helmut, additional, Schweitzer, Christophe, additional, Schuhbauer, Diana, additional, Reinhardt, Dieter, additional, Fischer, Christophe, additional, Diener, Catherine, additional, McArthur, Silvia Gatti, additional, Beck, Jennifer, additional, Wettstein, Joseph G., additional, Loetscher, Hansruedi, additional, Prinssen, Eric, additional, and Brockhaus, Manfred, additional

Published
2008
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