New considerations for hiPSC-based models of neuropsychiatric disorders

Molecular Psychiatry
Gabriel E HoffmanKristen J Brennand

Abstract

The development of human-induced pluripotent stem cells (hiPSCs) has made possible patient-specific modeling across the spectrum of human disease. Here, we discuss recent advances in psychiatric genomics and post-mortem studies that provide critical insights concerning cell-type composition and sample size that should be considered when designing hiPSC-based studies of complex genetic disease. We review recent hiPSC-based models of SZ, in light of our new understanding of critical power limitations in the design of hiPSC-based studies of complex genetic disorders. Three possible solutions are a movement towards genetically stratified cohorts of rare variant patients, application of CRISPR technologies to engineer isogenic neural cells to study the impact of common variants, and integration of advanced genetics and hiPSC-based datasets in future studies. Overall, we emphasize that to advance the reproducibility and relevance of hiPSC-based studies, stem cell biologists must contemplate statistical and biological considerations that are already well accepted in the field of genetics. We conclude with a discussion of the hypothesis of biological convergence of disease-through molecular, cellular, circuit, and patient level phenoty...Continue Reading

References

Dec 20, 2003·Annals of the New York Academy of Sciences·David A LewisRobert A Sweet
Feb 20, 2004·The International Journal of Neuropsychopharmacology·Oliver D HowesRobin M Murray
Apr 27, 2007·PloS One·Daniel StockholmAndras Paldi
Dec 8, 2007·Genome Research·Rohan B H WilliamsPeter F R Little
Jul 3, 2009·Nature·UNKNOWN International Schizophrenia ConsortiumPamela Sklar
Mar 9, 2010·Nature Methods·Shai S Shen-OrrAtul J Butte
May 21, 2010·Nature Reviews. Neuroscience·Maria KarayiorgouJoseph A Gogos
Feb 5, 2011·Nature·Ryan E MillsUNKNOWN 1000 Genomes Project
Apr 15, 2011·Nature·Kristen J BrennandFred H Gage
Jul 9, 2011·Nature Biotechnology·Dirk HockemeyerRudolf Jaenisch
Mar 28, 2012·Schizophrenia Bulletin·Elliott ReesMichael J Owen
Apr 11, 2012·Molecular Psychiatry·J L RapoportN Gogtay
May 9, 2012·Cell Stem Cell·Shila MekhoubadKevin Eggan
Jun 12, 2012·Neuron·Francis J McMahon, Thomas R Insel
Jul 5, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jessica MarianiFlora M Vaccarino
Sep 22, 2012·Nature·Michael J HawrylyczAllan R Jones
Dec 19, 2012·Cell Stem Cell·Qiurong DingChad A Cowan
Jun 25, 2013·Nature Biotechnology·Yanfang FuJeffry D Sander
Jul 23, 2013·Nature Biotechnology·Patrick D HsuFeng Zhang
Aug 13, 2013·Nature Genetics·UNKNOWN Cross-Disorder Group of the Psychiatric Genomics ConsortiumUNKNOWN International Inflammatory Bowel Disease Genetics Consortium (IIBDGC)
Sep 17, 2013·Biotechnology Advances·Jincheng Wu, Emmanuel S Tzanakakis
Oct 1, 2013·Nature Methods·Karin B MichelsRafael A Irizarry
Oct 19, 2013·Science·Maya KasowskiMichael Snyder
Dec 10, 2013·Cell Stem Cell·Justine D MillerLorenz Studer
Jan 28, 2014·Nature·Menachem FromerMichael C O'Donovan
Jan 28, 2014·Nature·Shaun M PurcellPamela Sklar
Feb 11, 2014·Neuron·Jonathan Flint, Kenneth S Kendler
Mar 1, 2014·The American Journal of Psychiatry·Maude SchneiderUNKNOWN International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome
Mar 13, 2014·Harvard Review of Psychiatry·Michael E TalkowskiJames F Gusella

❮ Previous
Next ❯

Citations

Nov 13, 2019·FEBS Letters·Larissa TraxlerJerome Mertens
Mar 4, 2020·Stem Cells and Development·Alejandro De Los Angeles, Elizabeth M Tunbridge
Feb 9, 2020·Cells·Anke HoffmannDietmar Spengler
May 8, 2020·Journal of Neural Transmission·Rhiannon V McNeillSarah Kittel-Schneider
Sep 25, 2019·Nature Genetics·Nadine SchrodeKristen J Brennand
Oct 5, 2019·International Journal of Molecular Sciences·Anke HoffmannDietmar Spengler
Apr 16, 2020·Molecular Autism·Ralda Nehme, Lindy E Barrett
May 20, 2020·Molecular Psychiatry·Chen ZhangMing Li
Apr 23, 2020·Current Psychiatry Reports·Debamitra DasDimitrios Avramopoulos
Jul 31, 2020·Bioinformatics·Gabriel E Hoffman, Panos Roussos
Jul 7, 2019·Schizophrenia Research·Prashanth RajarajanKristen J Brennand
Feb 9, 2020·Neuroscience and Biobehavioral Reviews·Stefan KloiberAndre F Carvalho
Jan 13, 2021·Nature Protocols·Nadine SchrodeKristen J Brennand
Feb 19, 2021·Translational Psychiatry·Santiago G LagoSabine Bahn
Mar 20, 2021·Journal of Tissue Engineering·Moshe J WillnerKam W Leong
Mar 26, 2021·Molecular Biology Reports·Laura da Silva SiqueiraDaniel Rodrigo Marinowic
Apr 4, 2021·International Journal of Molecular Sciences·Anke Hoffmann, Dietmar Spengler
May 20, 2021·Current Opinion in Neurobiology·Peter James Michael Deans, Kristen J Brennand
Jun 29, 2021·Biological Psychiatry·Alejandro De Los AngelesElizabeth M Tunbridge
Oct 17, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·Anastasia LevchenkoSvetlana A Ivanova
Aug 6, 2021·Brain, Behavior, and Immunity·Amalie C M CouchAnthony C Vernon
Aug 28, 2021·International Journal of Molecular Sciences·Dmitrii A AbashkinVera E Golimbet

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-seq
transfection

Software Mentioned

R
BrainSpan
variancePartition

Related Concepts

Related Feeds

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

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.