Gene expression profiling of MM cells treated with FGF-trap molecule NSC12
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE129279 | GEO | 2022/04/01
REPOSITORIES: GEO
Similar Datasets
Project description:Numerous studies have suggested a link between fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) signaling pathways; however the nature of this link has not been established. To evaluate this relationship we investigated VEGF signaling in endothelial cells with disrupted FGF signaling in vitro and in vivo. We find that endothelial cells lacking FGF signaling become unresponsive to VEGF due to down regulation of VEGFR2 expression caused by reduced Vegfr2 enhancer activation, which is in turn caused by reduced activation of Ets family transcription factors. In vivo this manifests in the loss of vascular integrity and morphogenesis. Thus, basal FGF stimulation of the endothelium is required for maintenance of VEGFR2 expression and the ability to respond to VEGF stimulation and accounts for the hierarchic control of vascular formation by FGFs and VEGF. Primary mouse lung endothelial cells were transduced with either Adeno-Null (empty) or Adeno- dominant negative FGF receptor 1 and harvested 24 hours after transduction. Total RNA was extracted and subjected to the analysis using SuperArray GEArray Q Series Mouse Angiogenesis Gene Array. Comparisons were made between treatments.
2011-06-07 | E-GEOD-28483 | biostudies-arrayexpress
Project description:Numerous studies have suggested a link between fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) signaling pathways; however the nature of this link has not been established. To evaluate this relationship we investigated VEGF signaling in endothelial cells with disrupted FGF signaling in vitro and in vivo. We find that endothelial cells lacking FGF signaling become unresponsive to VEGF due to down regulation of VEGFR2 expression caused by reduced Vegfr2 enhancer activation, which is in turn caused by reduced activation of Ets family transcription factors. In vivo this manifests in the loss of vascular integrity and morphogenesis. Thus, basal FGF stimulation of the endothelium is required for maintenance of VEGFR2 expression and the ability to respond to VEGF stimulation and accounts for the hierarchic control of vascular formation by FGFs and VEGF.
2011-06-07 | GSE28483 | GEO
Project description: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.
2023-03-24 | GSE228061 | GEO
Project description:A fundamental question in biology is how an undifferentiated field of cells acquires spatial pattern and undergoes coordinated differentiation. The development of the vertebrate limb is an important paradigm for understanding these processes. The skeletal and connective tissues of the developing limb all derive from a population of multipotent progenitor cells located in its distal tip. During limb outgrowth, these progenitors segregate into a chondrogenic lineage, located in the center of the limb bud, and soft connective tissue lineages located in its periphery. We report that the interplay of two families of signaling proteins, fibroblast growth factors (FGFs) and Wnts, coordinate the growth of the multipotent progenitor cells with their simultaneous segregation into these lineages. FGF and Wnt signals act together to synergistically promote proliferation while maintaining the cells in an undifferentiated, multipotent state, but act separately to determine cell lineage specification. Withdrawal of both signals results in cell cycle withdrawal and chondrogenic differentiation. Continued exposure to Wnt however, maintains proliferation and re-specifies the cells towards the soft connective tissue lineages. We have identified target genes that are synergistically regulated by Wnts and Fgfs, and show how these factors actively suppress differentiation and promote growth. Finally, we show how the spatial restriction of Wnt and FGF signals to the limb ectoderm and to a specialized region of it, the apical ectodermal ridge, controls the distribution of cell behaviors within the growing limb, and guides the proper spatial organization of the differentiating tissues. Keywords: transcriptional response to growth factor treatment Cells derived from mouse embryonic stage 11.5 limb buds were cultured and treated with purified Wnt3a protein or vehicle controls. The transcriptional response was detected using spotted cDNA microarrays after 2 hrs or 4 hrs of treatment. 4 biological replicates were used per condition.
2010-05-25 | E-GEOD-12441 | biostudies-arrayexpress
Project description:A fundamental question in biology is how an undifferentiated field of cells acquires spatial pattern and undergoes coordinated differentiation. The development of the vertebrate limb is an important paradigm for understanding these processes. The skeletal and connective tissues of the developing limb all derive from a population of multipotent progenitor cells located in its distal tip. During limb outgrowth, these progenitors segregate into a chondrogenic lineage, located in the center of the limb bud, and soft connective tissue lineages located in its periphery. We report that the interplay of two families of signaling proteins, fibroblast growth factors (FGFs) and Wnts, coordinate the growth of the multipotent progenitor cells with their simultaneous segregation into these lineages. FGF and Wnt signals act together to synergistically promote proliferation while maintaining the cells in an undifferentiated, multipotent state, but act separately to determine cell lineage specification. Withdrawal of both signals results in cell cycle withdrawal and chondrogenic differentiation. Continued exposure to Wnt however, maintains proliferation and re-specifies the cells towards the soft connective tissue lineages. We have identified target genes that are synergistically regulated by Wnts and Fgfs, and show how these factors actively suppress differentiation and promote growth. Finally, we show how the spatial restriction of Wnt and FGF signals to the limb ectoderm and to a specialized region of it, the apical ectodermal ridge, controls the distribution of cell behaviors within the growing limb, and guides the proper spatial organization of the differentiating tissues. Keywords: transcriptional response to growth factor treatment
2008-08-15 | GSE12441 | GEO
Project description:Vertebrate limbs develop by integrating signals that control patterning along three main orthogonal axes. Flank-produced retinoic acid (RA) is initially required for limb induction and establishment of the apical ectodermal ridge (AER), a distal signaling center that produces fibroblast growth factors (FGFs), which are essential for limb growth and distalization. Once the AER is established, RA:FGF antagonism determines the restricted expression of a set of genes that control limb proximodistal patterning. Essential for this antagonism is the activation by FGF of the RA-degrading enzyme CYP26B1 in the distal limb bud. In addition, sonic hedgehog produced from the zone of polarizing activity (ZPA) is essential for distal limb anteroposterior patterning and contributes to RA reduction by cooperating in CYP26B1 activation. Meis transcription factors are expressed in the proximal limb bud, are activated by RA and can regulate proximodistal limb development; however, the mechanisms underlying their activity remain unknown. Here we studied Meis function in the mouse limb bud through Meis2 conditional overexpression and elimination of Meis1 and Meis2. We found that Meis activity is first required for limb bud initiation and the proper establishment of the AER and ZPA signaling centers, and subsequently for the development of proximal limb structures. Functional genomic analyses reveal that Meis is an important conveyor of the RA:FGF antagonism through the regulation of components of the RA and FGF signaling pathways, including CYP26B1. In addition, Meis regulates a set of proximal limb genes controlling proximodistal patterning and differentiation. Our work reveals a regulatory module essential for limb patterning and potentially co-opted in other patterning processes involving RA:FGF antagonism.
2018-09-25 | GSE51374 | GEO
Project description:During limb development, fibroblast growth factors (FGFs) govern proximal-distal outgrowth and patterning. FGFs also synchronize developmental patterning between the proximal-distal and anterior-posterior axes by maintaining sonic hedgehog (SHH) expression in cells of the zone of polarizing activity (ZPA) in the distal posterior mesoderm. SHH, in turn, maintains FGFs in the apical ectodermal ridge (AER) which caps the distal tip of the limb bud. Crosstalk between FGF and SHH signaling is critical for patterned limb development, but the mechanisms underlying this feedback loop are not well characterized. Implantation of FGF beads in the proximal posterior limb bud can maintain SHH expression in the former ZPA domain (evident 3hrs after application), while prolonged exposure (24hrs) can induce SHH outside of this domain. Although temporally and spatially disparate, comparative analysis of transcriptome data from these different populations enriched molecules required for FGF-mediated SHH regulation.
2018-12-18 | GSE114661 | GEO
Project description:Individual signaling pathways, such as fibroblast growth factors (FGFs), can regulate a plethora of inductive events. According to current paradigms, signal-dependent transcription factors, such as FGF/MapK-activated Ets family factors, partner with lineage-determining factors to achieve regulatory specificity. However, many aspects of this model have not been rigorously investigated. One key question relates to whether lineage-determining factors dictate lineage-specific responses to inductive signals or facilitate these responses in collaboration with other inputs. We utilize the chordate model Ciona robusta to investigate mechanisms generating lineage-specific induction. Previous studies in C. robusta have shown that cardiopharyngeal progenitor cells are specified through the combined activity of FGF-activated Ets1/2.b and an inferred ATTA-binding transcriptional cofactor. Here we show that the homeobox transcription factor Lhx3/4 serves as the lineage-determining transcription factor that dictates cardiopharyngeal-specific transcription in response to pleiotropic FGF signaling. Targeted knockdown of Lhx3/4 leads to loss of cardiopharyngeal gene expression. Strikingly, ectopic expression of Lhx3/4 in a neuroectodermal lineage subject to FGF-dependent specification leads to ectopic cardiopharyngeal gene expression in this lineage. Furthermore, ectopic Lhx3/4 expression disrupts neural plate morphogenesis, generating aberrant cell behaviors associated with execution of incompatible morphogenetic programs. Based on these findings we propose that combinatorial regulation by signal-dependent and lineage-determinant factors represents a generalizable, previously uncategorized regulatory subcircuit we term cofactor-dependent induction. Integration of this subcircuit into theoretical models will facilitate accurate predictions regarding the impact of gene regulatory network rewiring on evolutionary diversification and disease ontogeny.
2023-12-21 | GSE250325 | GEO
Project description:The molecular basis for heterogeneity of cancer-associated fibroblast (CAF) populations remains to be established. We report that fibroblast growth factor (FGF) and transforming growth factor-beta (TGFB) signaling are strong opposite modulators of key CAF effector genes. While FGF activation in normal human dermal fibroblasts (HDFs) induces a number of mitogenic growth factors and metalloproteases, it suppresses expression of pro-fibrotic and cancer-associated extracellular matrix proteins, with TGFB exerting reverse effects. Genetic abrogation or pharmacological inhibition of either pathway results in induction of CAF effector genes responsive to the other, with the ETV1 transcription factor mediating FGF effects and suppressing those of TGFB. This duality of FGF- and TGFB- signaling is reflected in the distinct gene expression profiles of HDFs derived from a large cohort of individuals, multiple Squamous Cell Carcinoma (SCC)-derived CAF strains and stromal fibroblasts underlying premalignant (Actinic Keratoses) and desmoplastic versus non-desmoplastic skin SCC lesions. Functionally, an altered balance between FGF or TGFB signaling, by genetic suppression of either, is sufficient to confer upon HDFs growth enhancing properties on neighboring SCC cells, in vitro and in vivo, in an orthotopic skin cancer model. Thus, activation of heterogeneous CAF populations by deregulation of distinct signaling pathways converges on cancer development with implications of translational significance.
2019-07-31 | GSE122371 | GEO
Project description:The molecular basis for heterogeneity of cancer-associated fibroblast (CAF) populations remains to be established. We report that fibroblast growth factor (FGF) and transforming growth factor-beta (TGFB) signaling are strong opposite modulators of key CAF effector genes. While FGF activation in normal human dermal fibroblasts (HDFs) induces a number of mitogenic growth factors and metalloproteases, it suppresses expression of pro-fibrotic and cancer-associated extracellular matrix proteins, with TGFB exerting reverse effects. Genetic abrogation or pharmacological inhibition of either pathway results in induction of CAF effector genes responsive to the other, with the ETV1 transcription factor mediating FGF effects and suppressing those of TGFB. This duality of FGF- and TGFB- signaling is reflected in the distinct gene expression profiles of HDFs derived from a large cohort of individuals, multiple Squamous Cell Carcinoma (SCC)-derived CAF strains and stromal fibroblasts underlying premalignant (Actinic Keratoses) and desmoplastic versus non-desmoplastic skin SCC lesions. Functionally, an altered balance between FGF or TGFB signaling, by genetic suppression of either, is sufficient to confer upon HDFs growth enhancing properties on neighboring SCC cells, in vitro and in vivo, in an orthotopic skin cancer model. Thus, activation of heterogeneous CAF populations by deregulation of distinct signaling pathways converges on cancer development with implications of translational significance.
2019-07-31 | GSE122370 | GEO