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| Status |
Public on Nov 22, 2013 |
| Title |
Dynamic developmental signaling logic underlying lineage bifurcations during human endoderm induction and patterning from pluripotent stem cells [Endoderm RNA-seq and ChIP-seq data sets] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Unraveling complex signaling programs animating developmental lineage-decisions is pivotal to differentiate human pluripotent stem cells (hPSC) into pure populations of desired lineages for regenerative medicine. Developmental signals are strikingly temporally dynamic: BMP and Wnt initially specify primitive streak (progenitor to endoderm) yet 24 hours later suppress endoderm and induce mesoderm. At lineage bifurcations we show mutually-exclusive embryonic lineages are segregated through cross-repressive signals: TGFβ and BMP/MAPK duel to respectively specify pancreas versus liver from endoderm. Unilateral endodermal differentiation requires blockade of alternative fates at every stage, revealing a universal developmental strategy for efficient differentiation and anterior-posterior patterning of diverse hPSC lines into highly-pure endodermal populations. This culminated in hPSC-derived hepatic progenitors that, for the first time, engraft long-term in genetically-unconditioned mouse livers and secrete human albumin. Finally, thirty transcriptional and chromatin state maps capturing endoderm commitment revealed endodermal enhancers reside in an unanticipated diversity of "pre-enhancer" chromatin states before activation.
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| |
|
| Overall design |
Endoderm RNA-seq and ChIP-seq data sets
|
| |
|
| Contributor(s) |
Loh KM, Ang LT, Zhang J, Kumar V, Prabhakar S, Weissman IL, Lim B |
| Citation(s) |
24412311 |
| Submission date |
Nov 22, 2013 |
| Last update date |
Jul 28, 2020 |
| Contact name |
Kyle M. Loh |
| E-mail(s) |
kyleloh@stanford.edu
|
| Organization name |
Stanford University School of Medicine
|
| Department |
Department of Developmental Biology
|
| Street address |
265 Campus Drive
|
| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (36)
|
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| This SubSeries is part of SuperSeries: |
| GSE52658 |
Dynamic developmental signaling logic underlying lineage bifurcations during human endoderm induction and patterning from pluripotent stem cells |
|
| Relations |
| BioProject |
PRJNA229743 |
| SRA |
SRP033267 |
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