Brainstem Organoids From Human Pluripotent Stem Cells

Frontiers in Neuroscience
N. EuraEiichiro Mori

Abstract

The brainstem is a posterior region of the brain, composed of three parts, midbrain, pons, and medulla oblongata. It is critical in controlling heartbeat, blood pressure, and respiration, all of which are life-sustaining functions, and therefore, damages to or disorders of the brainstem can be lethal. Brain organoids derived from human pluripotent stem cells (hPSCs) recapitulate the course of human brain development and are expected to be useful for medical research on central nervous system disorders. However, existing organoid models are limited in the extent hPSCs recapitulate human brain development and hence are not able to fully elucidate the diseases affecting various components of the brain such as brainstem. Here, we developed a method to generate human brainstem organoids (hBSOs), containing midbrain/hindbrain progenitors, noradrenergic and cholinergic neurons, dopaminergic neurons, and neural crest lineage cells. Single-cell RNA sequence (scRNA-seq) analysis, together with evidence from proteomics and electrophysiology, revealed that the cellular population in these organoids was similar to that of the human brainstem, which raises the possibility of making use of hBSOs in investigating central nervous system disorde...Continue Reading

References

May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·O Saucedo-CardenasO M Conneely
Jan 1, 1999·Trends in Pharmacological Sciences·J J Soghomonian, D L Martin
Dec 10, 2002·Annual Review of Physiology·Richard B Robinson, Steven A Siegelbaum
Apr 23, 2004·Trends in Neurosciences·Robert T FremeauRobert H Edwards
Jan 28, 2006·Cell·Elisabet AnderssonJohan Ericson
May 3, 2006·Development·Samuel T Waters, Mark Lewandoski
Jun 9, 2009·Journal of Neuroendocrinology·N F DíazI Camacho-Arroyo
Jul 9, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mianzhi TangEric J Huang
Apr 9, 2011·Nature·Mototsugu EirakuYoshiki Sasai
May 17, 2011·Neural Development·Maria T M Alves dos Santos, Marten P Smidt
Mar 31, 2012·Brain Structure & Function·Ruth L StornettaPatrice G Guyenet
Apr 28, 2012·Journal of Neurochemistry·Andreas RatzkaClaudia Grothe
Jun 19, 2012·Cell Stem Cell·Tokushige NakanoYoshiki Sasai
Sep 8, 2012·Nature·Mark B GersteinMichael Snyder
May 30, 2013·Nature Genetics·UNKNOWN GTEx Consortium
Jul 11, 2013·BMC Bioinformatics·Jianqiang SunKoji Kadota
Sep 3, 2013·Nature·Madeline A LancasterJuergen A Knoblich
Nov 5, 2013·Progress in Neurobiology·Chao HeZhian Hu
Dec 12, 2013·Journal of Molecular Cell Biology·Wolfgang Wurst, Nilima Prakash
Jul 25, 2014·PLoS Computational Biology·Rekin's JankyStein Aerts
Sep 5, 2014·Nature Protocols·Madeline A Lancaster, Juergen A Knoblich
Jan 24, 2015·Science·Mathias UhlénFredrik Pontén
Apr 14, 2015·Nature Biotechnology·Rahul SatijaAviv Regev
Oct 28, 2015·FEBS Letters·Angela AndereggRajeshwar Awatramani
Jun 18, 2016·Cell·Hans Clevers
Jan 17, 2017·Nature Communications·Grace X Y ZhengJason H Bielas
May 13, 2017·Science·Peter J ThulEmma Lundberg
Aug 19, 2017·Science·Mathias UhlenFredrik Ponten

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Citations

Oct 6, 2020·Frontiers in Neurology·Benjamin GaletPhilippe Ravassard
Jan 16, 2021·Tissue Engineering. Part C, Methods·Renata Vieira de SáR Jeroen Pasterkamp
Dec 29, 2020·Frontiers in Cellular Neuroscience·Takeshi K MatsuiKen-Ichiro Kuwako
Jun 29, 2021·Frontiers in Physiology·Evanthia A Makrygianni, George P Chrousos
Jul 10, 2021·Stem Cell Reports·Parvin ValiulahiJae-Won Shim
Mar 24, 2021·Stem Cells·Takeshi K MatsuiKen-Ichiro Kuwako

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Datasets Mentioned

BETA
DRA009864
JPST000707
GSE145306

Methods Mentioned

BETA
PCR
Assay
Illumina sequencing
RNA-seq
scraping
protein assay
scRNA-Seq
Chip

Software Mentioned

AxoGraph
Mascot
R
STAR
Feature Mapper
AxoGraph X
Seurat
Ingenuity Pathway Analysis
Cell Ranger
Surat

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