Generation of self-organized sensory ganglion organoids and retinal ganglion cells from fibroblasts.

Science Advances
Dongchang XiaoMengqing Xiang

Abstract

Neural organoids provide a powerful tool for investigating neural development, modeling neural diseases, screening drugs, and developing cell-based therapies. Somatic cells have previously been reprogrammed by transcription factors (TFs) into sensory ganglion (SG) neurons but not SG organoids. We identify a combination of triple TFs Ascl1, Brn3b/3a, and Isl1 (ABI) as an efficient means to reprogram mouse and human fibroblasts into self-organized and networked induced SG (iSG) organoids. The iSG neurons exhibit molecular features, subtype diversity, electrophysiological and calcium response properties, and innervation patterns characteristic of peripheral sensory neurons. Moreover, we have defined retinal ganglion cell (RGC)-specific identifiers to demonstrate the ability for ABI to reprogram induced RGCs (iRGCs) from fibroblasts. Unlike iSG neurons, iRGCs maintain a scattering distribution pattern characteristic of endogenous RGCs. iSG organoids may serve as a model to decipher the pathogenesis of sensorineural diseases and screen effective drugs and a source for cell replacement therapy.

References

Jan 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·M XiangJ Nathans
Apr 30, 1996·Proceedings of the National Academy of Sciences of the United States of America·L GanJ Nathans
May 5, 1997·FEBS Letters·M OkabeY Nishimune
Jan 3, 2001·Nature Neuroscience·K L TuckerY A Barde
Feb 17, 2001·American Journal of Human Genetics·S A SlaugenhauptJ F Gusella
Dec 26, 2001·The Journal of Biological Chemistry·Eleanor Y M SumJane E Visvader
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jan 24, 2007·Nature Reviews. Neuroscience·Frédéric Marmigère, Patrik Ernfors
Oct 24, 2007·Trends in Neurosciences·Sulayman D Dib-HajjStephen G Waxman
May 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Xiuqian MuWilliam H Klein
Jul 26, 2008·PLoS Genetics·Tom Foulkes, John N Wood
Jan 29, 2010·Nature·Thomas VierbuchenMarius Wernig
Apr 2, 2011·Lancet·Harry A Quigley
May 28, 2011·Nature·Zhiping P PangMarius Wernig
Aug 20, 2011·Cell Stem Cell·Esther Y SonKevin Eggan
Jan 25, 2012·Nature Reviews. Neurology·Annelies RotthierKatrien Janssens
Apr 21, 2012·Trends in Neurosciences·Francois Lallemend, Patrik Ernfors
Sep 26, 2014·Stem Cell Reports·Soham ChandaMarius Wernig
Nov 25, 2014·Nature Neuroscience·Brian J WaingerClifford J Woolf
Nov 25, 2014·Nature Neuroscience·Joel W BlanchardKristin K Baldwin
May 26, 2015·Nature Genetics·Ya-Chun ChenJan Senderek
Jan 7, 2016·Nature·Tom BadenThomas Euler
Jan 29, 2016·Seminars in Cell & Developmental Biology·Adam Shellard, Roberto Mayor
Jan 17, 2017·Nature Communications·Grace X Y ZhengJason H Bielas
Aug 22, 2017·Nature Methods·Xiaojie QiuCole Trapnell
Jan 5, 2018·Nature Reviews. Gastroenterology & Hepatology·Robert O Heuckeroth
Mar 27, 2018·Stem Cell Reports·Kirstin B LangerJason S Meyer
May 11, 2018·Nature·Rachel TsunemotoKristin K Baldwin

❮ Previous
Next ❯

Citations

Sep 21, 2020·The British Journal of Ophthalmology·Alan Bird
Sep 29, 2020·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Alexios A Panoutsopoulos

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
scRNA-seq
RNA-seq
PCR
dissection
fluorescence-activated cell sorting
Chip
Assay

Software Mentioned

Excel
JuLI EDIT
GSEA
Patch Master
Seurat
Cell Ranger
Monocle
ImageJ
HCImage Live
Cufflinks

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

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.