Exam Details
Exam period:
Start: Friday October 27th at 12 pm (noon)
Due: Sunday October 29th at 12 pm (noon)
Format: Take home exam. Open book and on-line resources.
Exam Goal: Students will be given a task that will involve 2D or 3D cultures of human induced pluripotent
stem cells (h-iPSC) which will require experimental Kssue engineering design, interpretaKon of data
and possible artefacts, and design of an assay using the system that has been designed. The exam
will test the student’s scienKfic reasoning in designing and interpreKng experiments not in their
specific experKse.
Reading Material
I. Overview of iPSC models for Alzheimer’s disease (AD)
1. Barak, M., Fedorova, V., Pospisilova, V. et al. Human iPSC-Derived Neural Models for Studying
Alzheimer’s Disease: from Neural Stem Cells to Cerebral Organoids. Stem Cell Rev and Rep 18,
792–820 (2022). hZps://doi.org/10.1007/s12015-021-10254-3
II. Experimental Procedures for 3D Neuron-Microglia cultures from h-iPSCs
1. Abud EM, Ramirez RN, MarKnez ES, Healy LM, Nguyen CHH, Newman SA, Yeromin AV, Scarfone
VM, Marsh SE, Fimbres C, Caraway CA, Fote GM, Madany AM, Agrawal A, Kayed R, Gylys KH,
Cahalan MD, Cummings BJ, Antel JP, Mortazavi A, Carson MJ, Poon WW, Blurton-Jones M. iPSCDerived
Human Microglia-like Cells to Study Neurological Diseases. Neuron. 2017 Apr
19;94(2):278-293.e9. doi: 10.1016/j.neuron.2017.03.042
2. Haenseler W, Sansom SN, Buchrieser J, Newey SE, Moore CS, Nicholls FJ, Chintawar S, Schnell C,
Antel JP, Allen ND, Cader MZ, Wade-MarKns R, James WS, Cowley SA. A Highly Efficient Human
Pluripotent Stem Cell Microglia Model Displays a Neuronal-Co-culture-Specific Expression
Profile and Inflammatory Response. Stem Cell Reports. 2017 Jun 6;8(6):1727-1742. doi:
10.1016/j.stemcr.2017.05.017.
3. Walsh RM, Harschnitz O, Ciceri G, Sneeboer M, MazuKs L, SeZy M, Zumbo P, Betel D, de WiZe
LD, Pe’er D, Studer L. Fully defined human pluripotent stem cell-derived microglia and tri-culture
system model C3 producKon in Alzheimer’s disease. Nat Neurosci. 2021 Mar;24(3):343-354. doi:
10.1038/s41593-020-00796-z.
III. PotenKal Experimental Artefacts
1. Yuan C, Gao J, Guo J, Bai L, Marshall C, Cai Z, Wang L, Xiao M. Dimethyl sulfoxide damages
mitochondrial integrity and membrane potenKal in cultured astrocytes. PLoS One. 2014 Sep
19;9(9):e107447. doi: 10.1371/journal.pone.0107447.
2. Brunner JW, Lammertse HCA, van Berkel AA, Koopmans F, Li KW, Smit AB, Toonen RF, Verhage
M, van der Sluis S. Power and opKmal study design in iPSC-based brain disease modelling. Mol
Psychiatry. 2023 Apr;28(4):1545-1556. doi: 10.1038/s41380-022-01866-3.
IV. Metabolic ShuZles of the CNS and AD
1. Mason S. Lactate ShuZles in NeuroenergeKcs-Homeostasis, Allostasis and Beyond. Front
Neurosci. 2017 Feb 2;11:43. doi: 10.3389/fnins.2017.00043.
2. Monsorno, K., Ginggen, K., Ivanov, A. et al. Loss of microglial MCT4 leads to defecKve synapKc
pruning and anxiety-like behavior in mice. Nat Commun 14, 5749 (2023).
hZps://doi.org/10.1038/s41467-023-41502-4