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| Status |
Public on Jan 27, 2022 |
| Title |
Reconstruction of dynamic regulatory networks reveals signaling-induced topology changes associated with germ layer specification |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Elucidating regulatory relationships between transcription factors (TFs) and target genes is fundamental to understanding how cells control their identity and behavior. To overcome the limited scope and scalability of experimental methods in mapping this control, computational GRN reconstruction methods have been developed to infer relationships from transcriptomic data. We developed a new computational GRN reconstruction tool called Epoch, which takes advantage of single-cell RNA sequencing to address a number of shortcomings of existing tools including low precision, low sensitivity, and the limited ability to describe network topology changes over time. We used Epoch to identify the dynamic networks and key transcriptional regulators underpinning directed differentiation of mouse embryonic stem cells, and further demonstrate that modulating signaling pathways drives topological network changes that shape cell fate potential. By integrating signaling pathways with GRN structures, we traced how Wnt activation and PI3K suppression govern mesoderm and endoderm specification, respectively.
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| Overall design |
We perform single-cell RNA-sequencing on five time points spanning day 0 through day 4 of mouse embryonic stem cell day 0 through day 4 using the MULTI-seq protocol for sample multiplexing.
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| Contributor(s) |
Su EY, Spangler A, Cahan P |
| Citation(s) |
35090587 |
| |
| Submission date |
Jun 11, 2021 |
| Last update date |
Feb 23, 2022 |
| Contact name |
Patrick Cahan |
| E-mail(s) |
patrick.cahan@jhmi.edu
|
| Organization name |
Johns Hopkins University School of Medicine
|
| Department |
ICE and Biomedical Engineering
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| Lab |
Cahan Lab
|
| Street address |
733 North Broadway, MRB 653
|
| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21205 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (1) |
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| Relations |
| BioProject |
PRJNA736973 |
| SRA |
SRP323746 |
