Single-cell trajectory analysis of human homogenous neurons carrying a rare RELN variant

Translational Psychiatry
Yuko AriokaNorio Ozaki

Abstract

Reelin is a protein encoded by the RELN gene that controls neuronal migration in the developing brain. Human genetic studies suggest that rare RELN variants confer susceptibility to mental disorders such as schizophrenia. However, it remains unknown what effects rare RELN variants have on human neuronal cells. To this end, the analysis of human neuronal dynamics at the single-cell level is necessary. In this study, we generated human-induced pluripotent stem cells carrying a rare RELN variant (RELN-del) using targeted genome editing; cells were further differentiated into highly homogeneous dopaminergic neurons. Our results indicated that RELN-del triggered an impaired reelin signal and decreased the expression levels of genes relevant for cell movement in human neurons. Single-cell trajectory analysis revealed that control neurons possessed directional migration even in vitro, while RELN-del neurons demonstrated a wandering type of migration. We further confirmed these phenotypes in neurons derived from a patient carrying the congenital RELN-del. To our knowledge, this is the first report of the biological significance of a rare RELN variant in human neurons based on individual neuron dynamics. Collectively, our approach shoul...Continue Reading

References

Nov 1, 1991·The American Journal of Psychiatry·K L DavisM Davidson
May 26, 1995·Brain Research. Developmental Brain Research·H KawanoI Nagatsu
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·F ImpagnatielloE Costa
Mar 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·H M KimK Sugaya
Jun 5, 2003·Nature Reviews. Neuroscience·Fadel Tissir, André M Goffinet
Jul 27, 2005·Journal of Structural Biology·I F Sbalzarini, P Koumoutsakos
Mar 28, 2009·Schizophrenia Bulletin·Oliver D Howes, Shitij Kapur
Jan 8, 2010·Current Opinion in Neurobiology·Manuel Valiente, Oscar Marín
Feb 9, 2010·Trends in Neurosciences·Alain Chédotal
Jun 10, 2011·Nature Biotechnology·Kristen Martins-TaylorRen-He Xu
Jul 7, 2011·Cell·Jan H LuiArnold R Kriegstein
Jul 5, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jessica MarianiFlora M Vaccarino
Sep 18, 2012·Neuropharmacology·Timothy D Folsom, S Hossein Fatemi
Aug 14, 2013·Annual Review of Cell and Developmental Biology·Irina EvsyukovaE S Anton
Jan 28, 2014·Nature·Menachem FromerMichael C O'Donovan
Apr 2, 2014·Molecular Psychiatry·K BrennandF H Gage
Jul 18, 2014·Nature Protocols·Roman Gorelik, Alexis Gautreau
Nov 5, 2014·Nature·Silvia De RubeisJoseph D Buxbaum
Nov 25, 2014·Cell and Tissue Research·Ahmed SharafEleni Roussa
Nov 4, 2015·Methods : a Companion to Methods in Enzymology·Hongmei Lisa LiAkitsu Hotta
Apr 12, 2016·Frontiers in Cellular Neuroscience·Dawn B Lammert, Brian W Howell
Jun 1, 2016·Molecular Psychiatry·I KushimaN Ozaki
Nov 3, 2016·Frontiers in Cellular Neuroscience·Kazuhiro IshiiKazunori Nakajima
Mar 7, 2017·Nature Cell Biology·Johanna LiljaJohanna Ivaska
Jul 12, 2017·Journal of Neuroscience Methods·Yohei BambaMami Yamasaki

❮ Previous
Next ❯

Citations

Feb 18, 2020·Psychiatry and Clinical Neurosciences·Masahito SawahataNorio Ozaki
Sep 6, 2020·Journal of Molecular Neuroscience : MN·Sadiatul MarzanMohammad Safiqul Islam
Jul 24, 2020·Translational Psychiatry·Mariko SekiguchiNorio Ozaki
Aug 28, 2021·International Journal of Molecular Sciences·Dmitrii A AbashkinVera E Golimbet
Aug 28, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Masahito SawahataKiyofumi Yamada
Sep 28, 2021·Neurological Research·Xi-Qin FangXue-Wu Liu

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Software Mentioned

CCTop
ImageJ
RELN
MATLAB
del

Related Concepts

Related Feeds

Actin, Myosin & Cell Movement

Contractile forces generated by the actin-myosin cytoskeleton are critical for morphogenesis, but the cellular and molecular mechanisms of contraction have been elusive for many cell shape changes and movements. Here is the latest research on the roles of actin and myosin in cell movement.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cell Adhesion Molecules in the Brain

Cell adhesion molecules found on cell surface help cells bind with other cells or the extracellular matrix to maintain structure and function. Here is the latest research on their role in the brain.

Related Papers

Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society
Patrick T HarrisonUlrich Martin
Development, Growth & Differentiation
Takashi Yamamoto, Harukazu Nakamura
© 2022 Meta ULC. All rights reserved