Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Asymmetric crosstalk between the BMP and TGFβ pathways resolves signaling ambiguity

ABSTRACT: The BMP and TGFβ signaling pathways control cellular fate decisions in diverse biological contexts, often playing opposing roles. Despite extensive knowledge of these pathways, understanding how cells respond to environments containing these opposing cues remains a challenge. Here, we systematically analyze the activation of these pathways under combinatorial signaling environments. We find that TGFβ ligands inhibit BMP signaling, while BMP ligands enhance TGFβ transcriptional response across concentrations, ligand variants, and cell types. This asymmetric crosstalk results in the activation of a TGFβ-biased transcriptional response, even under mixed signaling conditions, effectively reducing signal ambiguity, with implications for processes such as EMT. We show that this crosstalk originates downstream of SMAD proteins phosphorylation. Using mathematical models, we predict, and experimentally verify, that promiscuous interactions between SMAD proteins provide the mechanism for the observed crosstalk. Our findings challenge the canonical models, suggesting an active role for mediator proteins in determining biological responses.

ORGANISM(S): Mus musculus

PROVIDER: GSE254418 | GEO | 2024/12/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

BMP/Taz-Hippo signaling modulates VEGF-mediated angiogenesis

Project description:The BMP/TGFβ-Smad, Notch and VEGF signaling guides formation of endothelial tip and stalk cells. However, the crosstalk of bone morphogenetic proteins (BMPs) and vascular endothelial growth factor receptor 2 (VEGFR2) signaling has remained largely unknown. We demonstrate that BMP family members regulate VEGFR2 and Notch signaling, and act via TAZ-Hippo signaling pathway. BMPs were found to be regulated after VEGF gene transfer in C57/Bl6 mice and in a porcine myocardial ischemia model. BMPs 2/4/6 were identified as endothelium-specific targets of VEGF. BMP2 modulated VEGF-mediated endothelial sprouting via Delta like Canonical Notch Ligand 4 (DLL4). BMP6 modulated VEGF signaling by regulating VEGFR2 expression and acted via Hippo signaling effector TAZ, known to regulate cell survival/proliferation, and to be dysregulated in cancer. In a matrigel plug assay in nude mice BMP6 was further demonstrated to induce angiogenesis. BMP6 is the first member of BMP family found to directly regulate both Hippo signaling and neovessel formation. It may thus serve as a target in pro/anti-angiogenic therapies.

2020-10-07 | GSE82106 | GEO

State- and stimulus-specific dynamics of SMAD signaling determine fate decisions in individual cells

Project description:SMAD-mediated signaling regulates a broad range of cell fate decisions including apoptosis, cell cycle arrest and EMT. To elucidate how this relatively simple pathway realizes this complexity, we systematically investigate how SMAD-mediated responses are modulated by various ligands of the TGFβ family, and compare these ligand responses in quiescent and proliferating MCF10A cells.

2023-02-01 | GSE223670 | GEO

Asymmetric crosstalk between the BMP and TGFβ pathways resolves signaling ambiguity

Project description:Asymmetric crosstalk between the BMP and TGFβ pathways resolves signaling ambiguity

| PRJNA1070349 | ENA

Genome-wide mapping of Olig2 targets in primary oligodendrocytes

Project description:Myelination by oligodendrocytes in the central nervous system (CNS) is essential for proper brain function, yet the molecular determinants that control this process remain poorly understood. The basic helix-loop-helix transcription factors Olig1 and Olig2 promote myelination, whereas bone morphogenetic protein (BMP) and Wnt/?-catenin signaling inhibit myelination. Here we show that these opposing regulators of myelination are functionally linked by the Olig1/2 common target Smad-interacting protein-1 (Sip1). We demonstrate that Sip1 is an essential modulator of CNS myelination. Sip1 represses differentiation inhibitory signals by antagonizing BMP receptor-activated Smad activity while activating crucial oligodendrocyte-promoting factors. Importantly, a key Sip1-activated target, Smad7, is required for oligodendrocyte differentiation and partially rescues differentiation defects caused by Sip1 loss. Smad7 promotes myelination by blocking the BMP- and ?-catenin-negative regulatory pathways. Thus, our findings reveal that Sip1-mediated antagonism of inhibitory signaling is critical for promoting CNS myelination and point to new mediators for myelin repair. ChIP-seq was performed to identify Olig2 direct target genes in oligodendrocytes during oligodendrocyte differentiation.

2012-08-31 | E-GEOD-40506 | biostudies-arrayexpress

Gold Compound Induces Immune Suppression via AHR-TGF-β1 Signaling

Project description:Gold compounds containing planar N-heterocyclic (NHC) carbene ligands are potent aryl hydrocarbon receptor (AHR) ligands. Further studies with the lead compound (called MC3), show that MC3 activates TGFβ signaling while repressing CD4+ T-cell activation in vitro, in human and mouse T-cells, and in scurfy mouse, while repression of AHR activity or TGFβ-SMAD cascades compensated its immune suppressive function. The in-vivo induction of Tgfb1 expression was associated with reduced severity of the autoimmune markers.

2019-01-16 | GSE125146 | GEO

Expression data from Sip1 cKO and control mice spinal cord

Project description:Myelination by oligodendrocytes in the central nervous system (CNS) is essential for proper brain function, yet the molecular determinants that control this process remain poorly understood. The basic helix-loop-helix transcription factors Olig1 and Olig2 promote myelination, whereas bone morphogenetic protein (BMP) and Wnt/β-catenin signaling inhibit myelination. Here we show that these opposing regulators of myelination are functionally linked by the Olig1/2 common target Smad-interacting protein-1 (Sip1). We demonstrate that Sip1 is an essential modulator of CNS myelination. Sip1 represses differentiation inhibitory signals by antagonizing BMP receptor-activated Smad activity while activating crucial oligodendrocyte-promoting factors. Importantly, a key Sip1-activated target, Smad7, is required for oligodendrocyte differentiation and partially rescues differentiation defects caused by Sip1 loss. Smad7 promotes myelination by blocking the BMP- and β-catenin-negative regulatory pathways. Thus, our findings reveal that Sip1-mediated antagonism of inhibitory signaling is critical for promoting CNS myelination and point to new mediators for myelin repair. We carried out microarray profiling analysis in the Sip1 conditional KO (cKO) mouse spinal cord to detail the change of global gene expression. Sip1 c/c;Olig1-Cre mouse spinal cord was collected at P14 for RNA extraction and Affymetrix microarray analysis. Sip1 c/+;Olig1-Cre littermate spinal cord was used as the control.

2012-08-31 | E-GEOD-40510 | biostudies-arrayexpress

Distinct BMP-Smad Signaling Outputs Confer Diverse Functions in Dental Mesenchyme [RNA-seq]

Project description:The canonical bone morphogenetic protein (BMP) signaling pathway plays a crucial regulatory role in tooth development by activating Smad proteins to regulate gene expression. We previously identified an atypical canonical BMP signaling in dental mesenchyme that is Smad4-independent but Smad1/5-dependent. This study demonstrates that phosphorylated Smad1/5 (pSmad1/5) and Smad4 regulate distinct gene sets in dental mesenchyme. Real-time monitoring of BMP-Smad transcriptional activity revealed that Smad4-dependent canonical BMP signaling is restricted to neurovascular cells surrounding the condensed dental mesenchymal cells where pSmad1/5 is present. Notably, pSmad1/5 in dental mesenchymal cells form complexes with pSmad3 to prevent canonical BMP signaling. CUT&RUN assays revealed genome-wide co-occupancy of pSmad1/5 and pSmad3, indicating their function as transcriptional regulation units. Integrative analyses demonstrated that this atypical canonical BMP signaling regulates tooth sensory innervation and maintains odontogenic inductive potential in dental mesenchyme, enabling the identification of critical genes for maintaining tooth inductive capability. Our findings elucidate the operating mechanism of atypical canonical BMP signaling in dental mesenchymal cells and clarify how BMP-Smad signaling exerts diverse functions across different cell types, informing future tooth bioengineering strategies.

2025-06-05 | GSE297137 | GEO

Distinct BMP-Smad Signaling Outputs Confer Diverse Functions in Dental Mesenchyme [CUT&Run]

2025-06-05 | GSE297033 | GEO

Distinct BMP-Smad Signaling Outputs Confer Diverse Functions in Dental Mesenchyme [ChIP-seq]

2025-06-05 | GSE296697 | GEO

Expression data from Sip1 cKO and control mice spinal cord

Project description:Myelination by oligodendrocytes in the central nervous system (CNS) is essential for proper brain function, yet the molecular determinants that control this process remain poorly understood. The basic helix-loop-helix transcription factors Olig1 and Olig2 promote myelination, whereas bone morphogenetic protein (BMP) and Wnt/β-catenin signaling inhibit myelination. Here we show that these opposing regulators of myelination are functionally linked by the Olig1/2 common target Smad-interacting protein-1 (Sip1). We demonstrate that Sip1 is an essential modulator of CNS myelination. Sip1 represses differentiation inhibitory signals by antagonizing BMP receptor-activated Smad activity while activating crucial oligodendrocyte-promoting factors. Importantly, a key Sip1-activated target, Smad7, is required for oligodendrocyte differentiation and partially rescues differentiation defects caused by Sip1 loss. Smad7 promotes myelination by blocking the BMP- and β-catenin-negative regulatory pathways. Thus, our findings reveal that Sip1-mediated antagonism of inhibitory signaling is critical for promoting CNS myelination and point to new mediators for myelin repair.

2012-08-31 | GSE40510 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data