Metformin rescues migratory deficits of cells derived from patients with periventricular heterotopia
Abstract: Periventricular neuronal heterotopia (PH) is one of the most common forms of cortical malformation in the human cortex. We show that human neuronal progenitor cells (hNPCs) derived from PH patients with a DCHS1 or FAT4 mutation as well as isogenic lines had altered migratory dynamics when grafted in the mouse brain. The affected migration was linked to altered autophagy as observed in vivo with an electron microscopic analysis of grafted hNPCs, a Western blot analysis of cortical organoids, and time‐lapse imaging of hNPCs in the presence of bafilomycin A1. We further show that deficits in autophagy resulted in the accumulation of paxillin, a focal adhesion protein involved in cell migration. Strikingly, a single‐cell RNA‐seq analysis of hNPCs revealed similar expression levels of autophagy‐related genes. Bolstering AMPK‐dependent autophagy by metformin, an FDA‐approved drug, promoted migration of PH patients‐derived hNPCs. Our data indicate that transcription‐independent homeostatic modifications in autophagy contributed to the defective migratory behavior of hNPCs in vivo and suggest that modulating autophagy in hNPCs might rescue neuronal migration deficits in some forms of PH.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Metformin rescues migratory deficits of cells derived from patients with periventricular heterotopia ; day:23 ; month:08 ; year:2023 ; extent:15
EMBO molecular medicine / European Molecular Biology Organization ; (23.08.2023) (gesamt 15)
- Urheber
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Bressan, Cedric
Snapyan, Marta
Snapyan, Marina
Klaus, Johannes
di Matteo, Francesco
Robertson, Stephen P.
Treutlein, Barbara
Parent, Martin
Cappello, Silvia
Saghatelyan, Armen
- DOI
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10.15252/emmm.202216908
- URN
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urn:nbn:de:101:1-2023082315212607723842
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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14.08.2025, 10:51 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Bressan, Cedric
- Snapyan, Marta
- Snapyan, Marina
- Klaus, Johannes
- di Matteo, Francesco
- Robertson, Stephen P.
- Treutlein, Barbara
- Parent, Martin
- Cappello, Silvia
- Saghatelyan, Armen
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