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  cultured embryonic stem cells[DCX-][BG121099]

Overall DesignThe transcriptomes of 1846 single cells were profiled by SmartSeq2 at different timepoints throughout a 54-day differentiation protocol that converted H1 human embryonic stem cells to a variety of brain cell types. Some cells were positively labeled by a expression of a barcoded viral transgene to help establish clonality (marked by an SK).
SummaryDuring development of the human brain, multiple cell types with diverse regional identities are generated. Here we report a system to generate early human brain forebrain and mid/hindbrain cell types from human embryonic stem cells (hESCs), and infer and experimentally confirm a lineage tree for the generation of these types based on single-cell RNA-Seq analysis. We engineered SOX2Cit/+ and DCXCit/Y hESC lines to target progenitors and neurons throughout neural differentiation for single-cell transcriptomic profiling, then identified discrete cell types consisting of both rostral (cortical) and caudal (mid/hindbrain) identities. Direct comparison of the cell types were made to primary tissues using gene expression atlases and fetal human brain single-cell gene expression data, and this established that the cell types resembled early human brain cell types, including preplate cells. From the single-cell transcriptomic data a Bayesian algorithm generated a unified lineage tree, and predicted novel regulatory transcription factors. The lineage tree highlighted a prominent bifurcation between cortical and mid/hindbrain cell types, confirmed by clonal analysis experiments. We demonstrated that cell types from either branch could preferentially generated by manipulation of the canonical Wnt/beta-catenin pathway. In summary, we present an experimentally validated lineage tree that encompasses multiple brain regions, and our work sheds light on the molecular regulation of region-specific neural lineages during human brain development. During development of the human brain, multiple cell types with diverse regional identities are generated. Here we report a system to generate early human brain forebrain and mid/hindbrain cell types from human embryonic stem cells (hESCs), and infer and experimentally confirm a lineage tree for the generation of these types based on single-cell RNA-Seq analysis. We engineered SOX2Cit/+ and DCXCit/Y hESC lines to target progenitors and neurons throughout neural differentiation for single-cell transcriptomic profiling, then identified discrete cell types consisting of both rostral (cortical) and caudal (mid/hindbrain) identities. Direct comparison of the cell types were made to primary tissues using gene expression atlases and fetal human brain single-cell gene expression data, and this established that the cell types resembled early human brain cell types, including preplate cells. From the single-cell transcriptomic data a Bayesian algorithm generated a unified lineage tree, and predicted novel regulatory transcription factors. The lineage tree highlighted a prominent bifurcation between cortical and mid/hindbrain cell types, confirmed by clonal analysis experiments. We demonstrated that cell types from either branch could preferentially generated by manipulation of the canonical Wnt/beta-catenin pathway. In summary, we present an experimentally validated lineage tree that encompasses multiple brain regions, and our work sheds light on the molecular regulation of region-specific neural lineages during human brain development. During development of the human brain, multiple cell types with diverse regional identities are generated. Here we report a system to generate early human brain forebrain and mid/hindbrain cell types from human embryonic stem cells (hESCs), and infer and experimentally confirm a lineage tree for the generation of these types based on single-cell RNA-Seq analysis. We engineered SOX2Cit/+ and DCXCit/Y hESC lines to target progenitors and neurons throughout neural differentiation for single-cell transcriptomic profiling, then identified discrete cell types consisting of both rostral (cortical) and caudal (mid/hindbrain) identities. Direct comparison of the cell types were made to primary tissues using gene expression atlases and fetal human brain single-cell gene expression data, and this established that the cell types resembled early human brain cell types, including preplate cells. From the single-cell transcriptomic data a Bayesian algorithm generated a unified lineage tree, and predicted novel regulatory transcription factors. The lineage tree highlighted a prominent bifurcation between cortical and mid/hindbrain cell types, confirmed by clonal analysis experiments. We demonstrated that cell types from either branch could preferentially generated by manipulation of the canonical Wnt/beta-catenin pathway. In summary, we present an experimentally validated lineage tree that encompasses multiple brain regions, and our work sheds light on the molecular regulation of region-specific neural lineages during human brain development.
Dataset viewGSE86982
PMIDNA

Samples in cultured embryonic stem cells[DCX-][BG121099]

Displaying 41-50 of 174 results.
SeriesSampleInstrumentOrganismTitleCell Source
GSE86982GSM2317332Illumina HiSeq 2500Homo sapiens26Dn4_B04_smart-seqcultured embryonic stem cells[DCX-][BG121099]
GSE86982GSM2317333Illumina HiSeq 2500Homo sapiens26Dn4_B05_smart-seqcultured embryonic stem cells[DCX-][BG121099]
GSE86982GSM2317334Illumina HiSeq 2500Homo sapiens26Dn4_B06_smart-seqcultured embryonic stem cells[DCX-][BG121099]
GSE86982GSM2317335Illumina HiSeq 2500Homo sapiens26Dn4_B07_smart-seqcultured embryonic stem cells[DCX-][BG121099]
GSE86982GSM2317336Illumina HiSeq 2500Homo sapiens26Dn4_B08_smart-seqcultured embryonic stem cells[DCX-][BG121099]
GSE86982GSM2317337Illumina HiSeq 2500Homo sapiens26Dn4_B09_smart-seqcultured embryonic stem cells[DCX-][BG121099]
GSE86982GSM2317338Illumina HiSeq 2500Homo sapiens26Dn4_B10_smart-seqcultured embryonic stem cells[DCX-][BG121099]
GSE86982GSM2317339Illumina HiSeq 2500Homo sapiens26Dn4_B11_smart-seqcultured embryonic stem cells[DCX-][BG121099]
GSE86982GSM2317340Illumina HiSeq 2500Homo sapiens26Dn4_C01_smart-seqcultured embryonic stem cells[DCX-][BG121099]
GSE86982GSM2317341Illumina HiSeq 2500Homo sapiens26Dn4_C02_smart-seqcultured embryonic stem cells[DCX-][BG121099]

Gene rank in cultured embryonic stem cells[DCX-][BG121099]

Displaying 21-30 of 23045 results.
Rank orderGene SymbolEnsembl ID
21RPS14ENSG00000164587
22RPL5ENSG00000122406
23c16_SSU-rRNA_Hsa
24TUBA1BENSG00000123416
25c1_LSU-rRNA_Hsa
26RPS3AENSG00000145425
27RPS3ENSG00000149273
28TPI1ENSG00000111669
29HNRNPA1ENSG00000135486
30UBBENSG00000170315