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| Status |
Public on Nov 08, 2021 |
| Title |
Changing the Waddington landscape to control mesendoderm competence -- ATAC-seq |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
As pluripotent human embryonic stem cells progress towards one germ layer fate, they lose the ability to adopt alternative fates. It is unknown how the cells’ competence for these alternative fates changes along their developmental trajectory or if this competence can be modulated. Here, we show that a differentiating stem cell’s probability of adopting a mesendodermal fate when given the appropriate signal falls sharply at a specific point along the ectodermal trajectory, and we further demonstrate that this point can be moved using genetic perturbations. Using a low-dimensional reaction coordinate to monitor progression towards ectoderm, we can determine the probability that individual cells at different points along this path can transition to the mesendodermal fate upon BMP4 and Activin A signal exposure. Knowing this probability allows us to prospectively isolate and profile differentiating cells based on their mesendoderm competence. Analysis and validation of these RNA-seq and ATAC-seq profiles identified transcription factors that can independently control the cell’s mesendoderm competence and its progression along the ectodermal developmental trajectory. In the classical picture of a Waddington landscape, these effects correspond to altering the barrier between fates and changing the cell’s location on the landscape, respectively. The ability of the underlying gene regulatory network to modulate these two aspects of the developmental landscape could allow separate control of the dynamics of differentiation and tissue size proportions.
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| Overall design |
ATAC-seq profiling of hESCs before and after they lose mesendoderm competence during ectoderm-differentiation, alongside a mesendoderm-derived outgroup to aid in the identification of fate-specific changes
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| Contributor(s) |
Valcourt JR, Huang R, Kundu S, Venkatasubramanian D, Kingston RE, Ramanathan S |
| Citation(s) |
34758327 |
| |
| Submission date |
Apr 21, 2020 |
| Last update date |
Dec 02, 2021 |
| Contact name |
Sharad Ramanathan |
| E-mail(s) |
sharad@cgr.harvard.edu
|
| Organization name |
Harvard University
|
| Department |
Molecular and Cellular Biology
|
| Lab |
Sharad Ramanathan's group
|
| Street address |
52 Oxford Street, Room 402
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02138 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (9)
|
| GSM4490153 |
pre_mesendo_competence_loss_ATACseq_rep1 |
| GSM4490154 |
post_mesendo_competence_loss_ATACseq_rep1 |
| GSM4490155 |
mesendo_derived_outgroup_ATACseq_rep1 |
| GSM4490156 |
pre_mesendo_competence_loss_ATACseq_rep2 |
| GSM4490157 |
post_mesendo_competence_loss_ATACseq_rep2 |
| GSM4490158 |
mesendo_derived_outgroup_ATACseq_rep2 |
| GSM4490159 |
pre_mesendo_competence_loss_ATACseq_rep3 |
| GSM4490160 |
post_mesendo_competence_loss_ATACseq_rep3 |
| GSM4490161 |
mesendo_derived_outgroup_ATACseq_rep3 |
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| This SubSeries is part of SuperSeries: |
| GSE149078 |
Changing the Waddington landscape to control mesendoderm competence |
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| Relations |
| BioProject |
PRJNA627245 |
| SRA |
SRP257800 |
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