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Report from the Edge of Neuroscience
Holmes, D.B.
2018
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citation for published version (APA)
Holmes, D. B. (2018). Report from the Edge of Neuroscience: Investigating an RNA Polymerase III related leukodystrophy using patient-derived iPSCs, neural cells, and mini-brains.
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The work described within was conducted at the Stem Cell Laboratory affiliated with the Department of Pediatrics/Child Neurology, VU University Medical Center, Amsterdam, The Netherlands; and the Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Amsterdam, Vrije Universiteit, Amsterdam, the Netherlands.
Research was supported by a ZonMw VIDI research grant (91712343 to V.M. Heine), ZonMw TAS IDB (116005006 to V.M. Heine), E-Rare Joint Call project (9003037601), KNAW Hersenstichting and Zeldzame Ziekten Fonds.
The Stem Cell Laboratory is an initiative of Prof. dr. M.S. van der Knaap.
Financial support for printing of this thesis was kindly provided by Stichting Researchfonds Kindergeneeskunde, VU University Medical Center, Amsterdam, The Netherlands.
ISBN: 978-94-6375-002-8
Cover design: Dwayne Holmes & Ridderprint BV, the Netherlands Printing: Ridderprint BV, the Netherlands
About the cover: processed ICC staining images of organoids (mini-brains)
VRIJE UNIVERSITEIT
Report from the Edge of Neuroscience
Investigating an RNA Polymerase III related leukodystrophy using
patient-derived iPSCs, neural cells, and mini-brains
ACADEMISCH PROEFSCHRIFT
ter verkrijging van de graad Doctor of Philosophy
aan de Vrije Universiteit Amsterdam,
op gezag van de rector magnificus
prof.dr. V. Subramaniam,
in het openbaar te verdedigen
ten overstaan van de promotiecommissie
van de Faculteit der Geneeskunde
op dinsdag 5 juni 2018 om 9.45 uur
in de aula van de universiteit,
De Boelelaan 1105
door
Dwayne Brandon Holmes
geboren te Illinois, Verenigde Staten
15566-DHolmes_BNW.indd 3 04-05-18 12:37
The work described within was conducted at the Stem Cell Laboratory affiliated with the Department of Pediatrics/Child Neurology, VU University Medical Center, Amsterdam, The Netherlands; and the Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Amsterdam, Vrije Universiteit, Amsterdam, the Netherlands.
Research was supported by a ZonMw VIDI research grant (91712343 to V.M. Heine), ZonMw TAS IDB (116005006 to V.M. Heine), E-Rare Joint Call project (9003037601), KNAW Hersenstichting and Zeldzame Ziekten Fonds.
The Stem Cell Laboratory is an initiative of Prof. dr. M.S. van der Knaap.
Financial support for printing of this thesis was kindly provided by Stichting Researchfonds Kindergeneeskunde, VU University Medical Center, Amsterdam, The Netherlands.
ISBN: 978-94-6375-002-8
Cover design: Dwayne Holmes & Ridderprint BV, the Netherlands Printing: Ridderprint BV, the Netherlands
About the cover: processed ICC staining images of organoids (mini-brains)
VRIJE UNIVERSITEIT
Report from the Edge of Neuroscience
Investigating an RNA Polymerase III related leukodystrophy using
patient-derived iPSCs, neural cells, and mini-brains
ACADEMISCH PROEFSCHRIFT
ter verkrijging van de graad Doctor of Philosophy
aan de Vrije Universiteit Amsterdam,
op gezag van de rector magnificus
prof.dr. V. Subramaniam,
in het openbaar te verdedigen
ten overstaan van de promotiecommissie
van de Faculteit der Geneeskunde
op dinsdag 5 juni 2018 om 9.45 uur
in de aula van de universiteit,
De Boelelaan 1105
door
Dwayne Brandon Holmes
geboren te Illinois, Verenigde Staten
15566-DHolmes_BNW.indd 3 04-05-18 12:37
promotor:
prof.dr. M.S. van der Knaap
copromotoren: dr. V.M. Heine
dr. N.I. Wolf
Table of Contents:
Chapter 1: Introduction
7
Chapter 2: Induced Pluripotent Stem Cells in Brain Diseases (excerpts)
21
Chapter 3: Patterning factors during neural progenitor induction
49
determine regional identity and differentiation potential
Chapter 4: Simplified 3D protocol capable of generating early cortical
71
neuroepithelium
Chapter 5: Streamlined 3D cerebellar differentiation protocol 85
with optional 2D modification
Chapter 6: iPSCs, cerebellar neurons and oligodendrocyte progenitor cells 107
derived from 4H leukodystrophy patients
Chapter 7: 4H leukodystrophy transcriptome analysis identifies POLR3B 119
transcriptional targets in iPSCs and disease phenotype-relevant
genes in cerebellar neurons
Chapter 8: Discussion
137
Summary
153
Acknowledgments
155
CV
157
15566-DHolmes_BNW.indd 4 04-05-18 12:37
