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| Status |
Public on Mar 24, 2023 |
| Title |
Population-level antagonism between FGF and BMP signaling steers mesoderm differentiation in embryonic stem cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The mesodermal precursor populations for different internal organ systems are specified during gastrulation by the combined activity of extracellular signaling systems such as BMP, Wnt, Nodal, and FGF. The BMP, Wnt and Nodal signaling requirements for the differentiation of specific mesoderm subtypes in mammals have been mapped in detail, but which mesodermal cell types depend on FGF signaling is not precisely known. It is also not clear how FGF signaling modulates the activity of orthogonal signaling systems involved in mesoderm differentiation. Here, we address these questions by analyzing the effects of targeted signaling manipulations in differentiating stem cell populations with single cell resolution. We identify opposing functions of BMP and FGF, and map the boundary between FGF-dependent and -independent mesodermal lineages. Stimulation with exogenous FGF boosts the expression of endogenous Fgfs while repressing Bmp ligands. This intercellular positive autoregulation of FGF signaling coupled to the repression of BMP signaling may contribute to the specification of reproducible and coherent cohorts of cells with the same identity via a community effect, both in the embryo and in synthetic embryo-like systems.
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| Overall design |
Mouse epiblast stem cells were differentiated towards a mix of mesodermal cell types in N2B27 medium supplemented with BMP4, CHIR99201 and different doses of FGF2 or the FGF receptor inhibitor AZD4547, and analyzed by scRNAseq.
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| Web link |
https://doi.org/10.1242/bio.059941
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| Contributor(s) |
Gattiglio M, Protzek M, Schröter C |
| Citation(s) |
37530863 |
| |
| Submission date |
Mar 23, 2023 |
| Last update date |
Aug 07, 2023 |
| Contact name |
Christian Schröter |
| E-mail(s) |
christian.schroeter@mpi-dortmund.mpg.de
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| Phone |
+492311332223
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| Organization name |
MPI of Molecular Physiology
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| Department |
Systemic Cell Biology
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| Street address |
Otto-Hahn-Str. 11
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| City |
Dortmund |
| State/province |
Nordrhein-Westfalen |
| ZIP/Postal code |
44227 |
| Country |
Germany |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA947968 |
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