Human SPG11 cerebral organoids reveal cortical neurogenesis impairment

Pérez-Brangulí F, Buchsbaum I, Pozner T, Regensburger M, Fan W, Schray A, Börstler T, Mishra HK, Gräf D, Kohl Z, Winkler J, Berninger B, Cappello S, Winner B (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Human Molecular Genetics Oxford University Press (OUP): Policy B - Oxford Open Option B

DOI: 10.1093/hmg/ddy397

Abstract

SPG11 linked hereditary spastic paraplegia is a complex monogenic neurodegenerative disease that in addition to spastic paraplegia is characterized by childhood onset cognitive impairment, thin corpus callosum and enlarged ventricles. We have previously shown impaired proliferation of SPG11 neural progenitor cells (NPCs). For delineation of potential defect in SPG11 brain development we employ 2D culture systems and 3D human brain organoids derived from SPG11 patients' iPSC and controls. We reveal that an increased rate of asymmetric divisions of neural progenitor cells leads to proliferation defect, causing premature neurogenesis. Correspondingly, SPG11 organoids appeared smaller than controls and had larger ventricles as well as thinner germinal wall. Premature neurogenesis and organoid size were rescued by GSK3-inhibititors including the FDA-approved tideglusib. These findings shed light on the neurodevelopmental mechanisms underlying disease pathology.

Authors with CRIS profile

Tatyana Pozner Professur für Stammzell-Modelle seltener neuraler Erkrankungen Martin Regensburger Interdisziplinäres Zentrum für Klinische Forschung IZKF-Förderlinien Tom Börstler Professur für Stammzell-Modelle seltener neuraler Erkrankungen Himanshu Kumar Mishra Department of Molecular Neurology Zacharias Kohl Department of Molecular Neurology Jürgen Winkler Professur für Molekulare Neurologie Beate Winner Professur für Stammzell-Modelle seltener neuraler Erkrankungen

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Max-Planck-Institut für Psychiatrie (Deutsche Forschungsanstalt für Psychiatrie) DE Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE)

How to cite

APA:

Pérez-Brangulí, F., Buchsbaum, I., Pozner, T., Regensburger, M., Fan, W., Schray, A.,... Winner, B. (2018). Human SPG11 cerebral organoids reveal cortical neurogenesis impairment. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddy397

MLA:

Pérez-Brangulí, Francesc, et al. "Human SPG11 cerebral organoids reveal cortical neurogenesis impairment." Human Molecular Genetics (2018).

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