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Series GSE185258 Query DataSets for GSE185258
Status Public on Feb 04, 2022
Title Signal requirement for cortical potential of transplantable human neuroepithelial stem cells [array]
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The cerebral cortex develops from dorsal forebrain neuroepithelial progenitor cells. Initial expansion of the progenitor cell pool is followed by the generation of neurons of all the cortical layers and later, astrocytes and oligodendrocytes. However, the regulatory pathways that control the expansion and maintenance of the neuroepithelial progenitor cell pool are currently unknown. Here we define six basic pathway components that regulate proliferation of cortically specified human neuroepithelial stem cells (cNESCs) in vitro without the loss of developmental potential. We show that activation of FGF and inhibition of BMP and ACTIVIN A signalling are required for long-term cNESC proliferation. We also demonstrate that cNESCs preserve dorsal telencephalon-specific potential when GSK3, AKT and nuclear CATENIN-b1 activity are low. Remarkably, regulation of these six pathway components supports the clonal expansion of cNESCs. Moreover, cNESCs differentiate to lower and upper layer cortical neurons both in vitro and in vivo. Identifying the mechanisms that drive the self-renewal and fate of cNESCs decision of neuroepithelial stem cells is key to developing new stem cell-based therapeutic approaches to treat neurological conditions.
In this study, we performed Oxford Nanopore technologies long-read RNA-sequencing (lrRNA-seq) of human cNESCs and of the human embryonic stem cells used to generate them. Two hESC cell lines were differentiated to cNESCs, which were then maintained in either six factors (6F : BMPRi, TGFBRi, GSK3i, FGF, TANKYRASEi, AKTi) or 4 factors (6F-2F : BMPRi, TGFBRi, GSK3i, FGF). All samples (hESCs, cNESCs in 6 factors, cNESCs in 4 factors) are submitted to lrRNA-seq as duplicates.
 
Overall design Balasz,V,Varga
 
Contributor(s) Khelifi G, Hussein SM, Nagy A
Citation(s) 35606347
Submission date Oct 04, 2021
Last update date Jun 01, 2022
Contact name Samer M.I. Hussein
E-mail(s) samer.hussein@fmed.ulaval.ca
Organization name CHU de Québec - Université Laval
Department Departement of medecine
Lab Hussein Lab
Street address 9 rue Mcmahon
City Quebec City
State/province Quebec
ZIP/Postal code G1R 3S3
Country Canada
 
Platforms (1)
GPL17586 [HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version]
Samples (28)
GSM5608867 CA1J cNES, biological replicate 1
GSM5608868 CA1J cNES, biological replicate 2
GSM5608869 H1JA cNES, biological replicate 1
Relations
BioProject PRJNA768415

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE185258_RAW.tar 713.3 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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