Ontology highlight
ABSTRACT:
PROVIDER: PRJNA625309 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Changing the Waddington landscape to control mesendoderm competence
| PRJNA627244 | ENA
Project description:Changing the Waddington landscape to control mesendoderm competence -- ATAC-seq
| PRJNA627245 | ENA
Project description:Changing the Waddington landscape to control mesendoderm competence -- RNA-seq
| PRJNA626448 | ENA
Project description: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.
2021-11-08 | GSE149077 | GEO
Project description: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.
2021-11-08 | GSE148904 | GEO
Project description:We sequenced human embryonic stem cells (hESCs), pre-mesendoderm cells (PreME) that acquire transient competence for PGCLC specification and cells at the mesendoderm (ME) stage when they are not longer PGC-competent.
2022-01-21 | E-MTAB-11135 | biostudies-arrayexpress
Project description:We have demonstrated that Meteor KO cells are associated with a global transcriptional reprogramming associated to a block of Mesendoderm specification. Meteor KO cells loses their developmental competence for Mesendoderm specification in pluripotency and are redirected to a neuroectoderm fate.
2017-10-10 | GSE103583 | GEO
Project description:We mapped the enhancer and long non-coding transcriptional landscape during mesendoderm specification. Mesendodermal progenitors were sorted from differentiating ESCs according to Eomes expression. Enhancer usage was coordinated with mesendoderm-specific expression of key lineage-determining transcription factors. We demonstrated that many of these enhancers are associated with the expression of lncRNAs.
2017-10-10 | GSE103262 | GEO
Project description:During gastrulation, dynamic interplay among cell signaling pathways dictates cell fate decisions. While extensive studies have elucidated their critical roles in morphological regulation, how these signals orchestrate the epigenome to confer developmental competence remains unclear. In this study, we demonstrate that H3K9me3-marked facultative heterochromatin domains undergo global reorganization during differentiation of human pluripotent stem cells (hPSCs) into mesendoderm (ME) and definitive endoderm (DE), which arise through epithelial-mesenchymal transition (EMT), but not into early neural ectoderm (NE), which retains epithelial state. We identify the MAPK/ERK pathway, acting downstream of FGF signaling, as a key mediator of this reorganization within a critical temporal window during hPSC-to-ME differentiation. Mechanistically, phosphorylated-ERK is enriched across chromatin domains spanning key developmental gene loci and exhibits a reciprocal genomic pattern with H3K9me3, which becomes ectopically accumulated upon MAPK/ERK inhibition. Furthermore, using CRISPRi-mediated perturbation of H3K9me3 methyltransferases, we reveal that proper establishment of H3K9me3 domains plays a dual role in repressing off-target genes and enabling robust activation of lineage-specific programs. Collectively, our findings reveal a previously unrecognized role for MAPK/ERK signaling in reorganizing the H3K9me3 landscape to confer developmental competence, providing mechanistic insight into how signaling pathways shape the epigenetic landscape during development.
2026-02-26 | GSE289666 | GEO
Project description:We mapped the enhancer and long non-coding transcriptional landscape during mesendoderm specification. Mesendodermal progenitors were sorted from differentiating ESCs according to Eomes expression. Enhancer usage was coordinated with mesendoderm-specific expression of key lineage-determining transcription factors. We demonstrated that many of these enhancers are associated with the expression of lncRNAs.
2017-10-10 | GSE103261 | GEO