Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA391161 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:SMAD4 impedes conversion of NK cells into ILC1-like cells by curtailing non-canonical TGFb signaling (mouse data sets)
| PRJNA391163 | ENA
Project description:SMAD4 impedes conversion of NK cells into ILC1-like cells by curtailing non-canonical TGFb signaling
| PRJNA391153 | ENA
Project description:Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from NK cells is a gene signature indicative of TGFb-family cytokine imprinting. To assess the impact of TGFb family cytokines on ILC1 differentation, we examined SMAD4- a transcription factor that facilitates the signaling pathway common to all TGFb family cytokines-was specifically ablated in ILCs and NK cells. While SMAD4 deficiency did not affect ILC1 differentation, NK cells paradoxically aquired an ILC1-like gene signature and were incapable of controlling tumor metastasis and viral infection. We used microarray to compare the transcriptional differences between human blood NK cells. NK cells from a patient with a deleterious SMAD4 mutation or control NK cells were cultured overnight with either IL-2 alone or TGFb1 and IL-2.
2017-07-31 | GSE100246 | GEO
Project description:Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from NK cells is a gene signature indicative of TGFb-family cytokine imprinting. To assess the impact of TGFb family cytokines on ILC1 differentation, we examined SMAD4- a transcription factor that facilitates the signaling pathway common to all TGFb family cytokines-was specifically ablated in ILCs and NK cells. While SMAD4 deficiency did not affect ILC1 differentation, NK cells paradoxically aquired an ILC1-like gene signature and were incapable of controlling tumor metastasis and viral infection. We used microarray to define the transcriptional differences between splenic NK cells from WT and SMAD4F/F x Ncr1-Cre mice.
2017-07-31 | GSE100247 | GEO
Project description:TGFb is a pleiotropic cytokine which can exert its regulatory effects on differentiation of cytotoxic T lymphocytes (CTLs) and alter their cell fate. Canonical TGFb signaling inhibits the formation of KLRG1+ effector cells and circulating memory cells while inducing the formation of resident memory cells. However, SMAD4 functions contradictory to TGFb where it is required for the formation of KLRG1+ effector cells and circulating memroy cells and actively inhibit the formation of resident memory cells. Using, RNA-Sequencing we identified that Smad4 alters the gene expression profile of pathogen-specific CTLs after intranasal infection with Listeria monocytogenes expressing chicken ovalbumin.
2022-10-04 | GSE214599 | GEO
Project description:The TGFb signaling pathway is a critical regulator of developmental processes and disease. We developed a system to measure TGFb signaling dynamics by monitoring the localization of Smad4. We performed an unbiased genome-wide RNAi screen to identify genes involved in ligand-dependent Smad4 nuclear translocation
2015-07-15 | GSE70924 | GEO
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 | GSE297033 | GEO
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 | GSE296697 | GEO
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
Project description:BMP (bone morphogenetic protein) signaling plays essential roles in the regulation of early tooth development. It is well acknowledged that with binding of extracellular BMP ligands to the type I and type II transmembrane serine/threonine kinase receptor complexes when triggering of the BMP canonical signaling pathway, receptor activated Smad1/5/8 in cytoplasm bind to Smad4, the central mediator of the canonical BMP signaling pathway, to form transfer complexes for entering the nucleus and regulating target gene expression. However, our recent studies reveal the functional operation of a novel BMP mediated signaling pathway named as the atypical BMP canonical signaling pathway in mouse developing tooth, which is Smad1/5/8 dependent but Smad4 independent. In the current study, we investigated whether this atypical BMP canonical signaling is conserved in human odontogenesis. We showed that pSmad1/5/8 is required for expression of MSX1, a well-defined BMP signaling target gene, in human dental mesenchyme, but the typical BMP canonical signaling is indeed not operating in the early human developing tooth, as assessed by the absence of pSMAD1/5/8-SMAD4 complexes in the dental mesenchyme and expression of MSX1 and translocation of pSMAD1/5/8 induced by BMP4 protein is SMAD4-independent in dental mesenchymal cells. Moreover, RNA-Seq data sets comparing the transcriptome profiles of human dental mesenchymal cells with and without SMAD4 knockdown by siRNA displays unchanged expression profiles of pSMAD1/5/8 downstream target genes, further affirming the functional operation of the atypical canonical BMP signaling pathway in a manner of SMAD1/5/8-dependent but SMAD4-independent in the dental mesenchyme during early odontogenesis.
2021-09-30 | GSE179474 | GEO