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Series GSE139273 Query DataSets for GSE139273
Status Public on Jan 21, 2020
Title Transcriptional Programming of Human Mechanosensory Neuron Subtypes from Pluripotent Stem Cells
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary In vitro generation of human peripheral sensory neurons may provide a framework for novel drug screening platforms and disease models of touch and pain. However, derivation of a functionally pure sensory neuron population remains a major unmet challenge. We discovered that, by expressing the transcription factors NGN2 and BRN3A, human pluripotent stem cells can be induced to differentiate into a surprisingly homogenous culture of cold- and mechano-sensing neurons. Although such a neuronal subtype has not been reported in mice, we found molecular evidence of its existence in adult human sensory ganglia. Combining NGN2 and BRN3A programming with neural crest patterning, we produced two additional populations of sensory neurons, including a more specialized mechanosensory neuron subtype. Finally, we applied this system to model a rare inherited sensory disorder, characterized by profound impairment of touch sensation and proprioception, caused by inactivating mutations in PIEZO2. Together these findings establish an approach to specify distinct sensory neuron subtypes in vitro, underscoring the utility of stem cell technology to capture human-specific features of physiology and disease.
Overall design RNA sequencing was performed on a total of 13 human samples. Of these samples, one represented a pool of human Dorsal Root Ganglia (hDRG), three represented human undifferentiated induced pluripotent stem cells (iPSC), three represented sensory neurons induced by NGN2-BRN3A expression in iPSCs (iSN), three represented sensory neurons induced by long term NGN2-BRN3A expression in iPSC-derived neural crest (NC_iSN1), and three represented sensory neurons induced by short term NGN2-BRN3A expression in iPSC-derived neural crest (NC_iSN2).
Contributor(s) Nickolls AR, Lee MM, Espinoza DF, Szczot M, Lam R, Wang Q, Beers J, Zou J, Nguyen MQ, Solinski HJ, AlJanahi AA, Johnson KR, Ward ME, Chesler AT, Bönnemann CG
Citation(s) 31968264, 32423971
Submission date Oct 23, 2019
Last update date Jul 07, 2020
Contact name Kory R Johnson
Phone 301-402-1956
Organization name NINDS/NIH
Department DIR IT & Bioinformatics
Lab Bioinformatics Section
Street address 10/3B01, 9000 Rockville Pike
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (13)
GSM4135900 hDRG_Bioreplicate_1
GSM4135901 iPSC_Bioreplicate_1
GSM4135902 iPSC_Bioreplicate_2
BioProject PRJNA579052
SRA SRP226691

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Supplementary file Size Download File type/resource
GSE139273_RAW.tar 33.3 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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