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Status |
Public on Oct 17, 2017 |
Title |
Mouse embryonic stem cells can differentiate via multiple paths to the same state [RNA-seq] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
In embryonic development, cells must differentiate through stereotypical sequences of intermediate states to generate mature states of a particular fate. By contrast, direct programming can generate similar fates through alternative routes, by directly expressing terminal transcription factors. Yet the cell state transitions defining these new routes are unclear. We applied single-cell RNA sequencing to compare two mouse motor neuron differentiation protocols: a standard protocol approximating the embryonic lineage, and a direct programming method. Both undergo similar early neural commitment. Then, rather than transitioning through spinal intermediates like the standard protocol, the direct programming path diverges into a novel transitional state. This state has specific and abnormal gene expression. It opens a 'loop' or 'worm hole' in gene expression that converges separately onto the final motor neuron state of the standard path. Despite their different developmental histories, motor neurons from both protocols structurally, functionally, and transcriptionally resemble motor neurons from embryos.
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Overall design |
2 protocols were profiled at 3 timepoints each (samples 1-5), and compared to primary embryonic motor neurons (sample 6). Each sample contains 667-1,057 single-cell transcriptomes (total = 5,405).
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Contributor(s) |
Briggs JA, Li VC, Lee S, Woolf CJ, Klein AM, Kirschner MW |
Citation(s) |
28990928 |
Submission date |
Apr 04, 2017 |
Last update date |
May 15, 2019 |
Contact name |
James Alexander Briggs |
E-mail(s) |
james.briggs@uqconnect.edu.au
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Organization name |
Harvard Medical School
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Department |
Department of Systems Biology
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Lab |
Kirschner / Klein labs
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Street address |
200 Longwood Avenue, Harvard Medical School
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City |
Boston |
State/province |
Massachusetts |
ZIP/Postal code |
02115 |
Country |
USA |
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Platforms (3) |
GPL16417 |
Illumina MiSeq (Mus musculus) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (6)
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This SubSeries is part of SuperSeries: |
GSE97391 |
Mouse embryonic stem cells can differentiate via multiple paths to the same state |
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Relations |
BioProject |
PRJNA381617 |
SRA |
SRP103028 |
Supplementary file |
Size |
Download |
File type/resource |
GSE97390_E13.5_primary_motor_neuron.filtered_normalized_counts.csv.gz |
3.6 Mb |
(ftp)(http) |
CSV |
GSE97390_E13.5_primary_motor_neuron.raw_umifm_counts.csv.gz |
1.9 Mb |
(ftp)(http) |
CSV |
GSE97390_SPRING_combined_trajectories.filtered_normalized_counts.csv.gz |
32.5 Mb |
(ftp)(http) |
CSV |
GSE97390_direct_programming.filtered_normalized_counts.csv.gz |
26.1 Mb |
(ftp)(http) |
CSV |
GSE97390_direct_programming.raw_umifm_counts.csv.gz |
8.8 Mb |
(ftp)(http) |
CSV |
GSE97390_standard_protocol.filtered_normalized_counts.csv.gz |
28.2 Mb |
(ftp)(http) |
CSV |
GSE97390_standard_protocol.raw_umifm_counts.csv.gz |
8.9 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |