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| Status |
Public on Sep 30, 2016 |
| Title |
REGION-SPECIFIC NEURAL STEM CELL LINEAGES REVEALED BY SINGLE-CELL RNA-SEQ FROM HUMAN EMBRYONIC STEM CELLS [Cel-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
The transcriptomes of 2684 single cells were profiled by CelSeq at different timepoints throughout a 54-day differentiation protocol that converted H1 human embryonic stem cells to a variety of brain cell types.
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| Contributor(s) |
Yao Z, Mich JK, Ku S, Menon V, Krostag A, Martinez RA, Grimley JS, Wang Y, Ramanathan S, Levi BP |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Sep 15, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Zizhen yao |
| E-mail(s) |
zizheny@alleninstitute.org
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| Organization name |
Allen Institute for Brain Science
|
| Department |
MAT
|
| Street address |
551 N 34th St #200
|
| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98103 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (2684)
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| This SubSeries is part of SuperSeries: |
| GSE86894 |
REGION-SPECIFIC NEURAL STEM CELL LINEAGES REVEALED BY SINGLE-CELL RNA-SEQ FROM HUMAN EMBRYONIC STEM CELLS |
|
| Relations |
| BioProject |
PRJNA343284 |
| SRA |
SRP090072 |
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