Stem cell models of human synapse development and degeneration

Molecular Biology of the Cell
Emily S Wilson, Karen Newell-Litwa


Many brain disorders exhibit altered synapse formation in development or synapse loss with age. To understand the complexities of human synapse development and degeneration, scientists now engineer neurons and brain organoids from human-induced pluripotent stem cells (hIPSC). These hIPSC-derived brain models develop both excitatory and inhibitory synapses and functional synaptic activity. In this review, we address the ability of hIPSC-derived brain models to recapitulate synapse development and insights gained into the molecular mechanisms underlying synaptic alterations in neuronal disorders. We also discuss the potential for more accurate human brain models to advance our understanding of synapse development, degeneration, and therapeutic responses.


Jan 13, 2000·Archives of General Psychiatry·L A Glantz, D A Lewis
Jul 10, 2003·Lancet Neurology·Roberto Tuchman, Isabelle Rapin
Jan 7, 2004·Nature Reviews. Neuroscience·Rafael Yuste, Tobias Bonhoeffer
Sep 5, 2006·Neuropharmacology·Gary LynchChristine M Gall
Dec 26, 2006·Brain Research Reviews·W Y ChanP Rezaie
Feb 6, 2007·Current Opinion in Neurobiology·Ann Marie Craig, Yunhee Kang
May 9, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Robert A SweetDavid A Lewis
Apr 3, 2009·The Journal of Clinical Investigation·David A Lewis, Robert A Sweet
Oct 2, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Gregory Z Tau, Bradley S Peterson
Mar 20, 2010·Biochemical Society Transactions·Nils BrosePaul Skehel
Feb 18, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Anna R MooreSrdjan D Antic
Feb 25, 2011·Nature Neuroscience·P PenzesKevin M Woolfrey
Apr 15, 2011·Nature·Kristen BrennandFred H Gage
Jun 15, 2011·Cell·Ricardo E Dolmetsch, Daniel H Geschwind
Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Zdravko PetanjekIvica Kostovic
Aug 30, 2011·Molecular Neurodegeneration·Robert M KoffieTara L Spires-Jones
Jan 10, 2012·Cold Spring Harbor Perspectives in Medicine·Alberto Serrano-PozoBradley T Hyman
Jan 27, 2012·Nature·Mason A IsraelLawrence S B Goldstein
Sep 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Daniel J MillerChet C Sherwood
Feb 21, 2013·Frontiers in Neural Circuits·Ana M Estrada-Sánchez, George V Rebec
Jul 11, 2013·Nature Reviews. Neuroscience·Anthony J Koleske
Aug 9, 2013·Translational Neurodegeneration·Janet K KernMark R Geier
Sep 3, 2013·Nature·Madeline A LancasterJuergen A Knoblich
Nov 10, 2013·Nature Reviews. Neuroscience·Eric HanseIlse Riebe
Dec 10, 2013·Cell Stem Cell·Justine D MillerLorenz Studer
Apr 2, 2014·Molecular Psychiatry·Kristen BrennandFred H Gage
Aug 29, 2014·PloS One·Christina R MuratoreTracy L Young-Pearse
Nov 12, 2014·Molecular Psychiatry·K Griesi-OliveiraAlysson R Muotri
May 29, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sudhir SivakumaranTarek Z Deeb
Aug 19, 2015·Translational Psychiatry·L D Selemon, N Zecevic
Oct 2, 2015·Autism Research : Official Journal of the International Society for Autism Research·Michael W NestorGene J Blatt
Nov 28, 2015·Neuropathology and Applied Neurobiology·Arianna BellucciPierFranco Spano
Jan 7, 2016·Proceedings of the National Academy of Sciences of the United States of America·Xin TangGong Chen
Jun 4, 2016·Cell Stem Cell·Iva Kelava, Madeline A Lancaster
Jul 6, 2016·Molecular Psychiatry·Maria C MarchettoAlysson R Muotri
Dec 13, 2016·Molecular Neurodegeneration·Se Hoon ChoiDoo Yeon Kim
Jan 4, 2017·Cell Stem Cell·Yun LiRudolf Jaenisch
Mar 28, 2017·Scientific Reports·Rômulo Sperduto DezonneFlávia Carvalho Alcantara Gomes
Apr 21, 2017·Neuron·Edsel M AbudMathew Blurton-Jones
Apr 27, 2017·Nature·Giorgia QuadratoPaola Arlotta
Sep 8, 2017·Nature Reviews. Neuroscience·Elizabeth Di Lullo, Arnold R Kriegstein
Oct 14, 2017·Brain Sciences·Yukari Takarae, John Sweeney
Nov 2, 2017·Scientific Reports·Simon D KlapperVolker Busskamp
Nov 2, 2017·Translational Neurodegeneration·Panchanan MaitiGary L Dunbar
Nov 3, 2017·Neuron·Nicola J Allen, Cagla Eroglu
Nov 13, 2017·Molecular Neurobiology·Bruno H S AraujoEsper A Cavalheiro
Dec 3, 2017·The Journal of Cell Biology·David V HansenMorgan Sheng
Apr 17, 2018·Nature Biotechnology·Abed AlFatah MansourFred H Gage
May 16, 2018·Nature Physics·Eyal KarzbrunOrly Reiner
Jul 12, 2018·Proceedings of the National Academy of Sciences of the United States of America·Iryna ProtsBeate Winner
Jul 27, 2018·Nature Methods·Mayur MadhavanPaul J Tesar


Jul 28, 2020·Journal of Neuroscience Research·Emily S WilsonKaren Newell-Litwa
May 16, 2019·Assay and Drug Development Technologies·Alexis Papariello, Karen Newell-Litwa
Jun 9, 2020·Frontiers in Cell and Developmental Biology·Lisa Maria Smits, Jens Christian Schwamborn
Oct 7, 2020·Scientific Reports·Emily S WilsonKaren Newell-Litwa
Nov 9, 2019·Trends in Molecular Medicine·Daniel A BalikovEthan S Lippmann

Methods Mentioned

electron microscopy

Related Concepts

Cell Differentiation Process
Human Induced Pluripotent Stem Cells
Brain Diseases
Nerve Degeneration
Stem Cells

Related Feeds

Brain developing: Influences & Outcomes

This feed focuses on influences that affect the developing brain including genetics, fetal development, prenatal care, and gene-environment interactions. Here is the latest research in this field.

Brain Organoids in Disease Modeling

Brain organoids are three-dimensional cell culture models derived from human pluripotent stem cells. Since they resemble the embryonic brain, they can be used to help study brain biology, early brain development, and brain diseases. Discover the latest research on brain organoids in disease modeling here.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

3D Cellular Models of Brain and Neurodegeneration

Brain organoids are three-dimensional in vitro cellular models of the brain that can recapitulate many processes such as the neurodevelopment. In addition, these organoids can be combined with other cell types, such as neurons and astrocytes to study their interactions in assembloids. Disease processes can also be modeled by induced pluripotent stem cell-derived organoids and assembloids from patients with neurodegenerative disorders. Discover the latest research on the models here.