Role of Smad7 in Hematopoietic (M-O7e) and Non-Hematopoietic (PG13) Stem Cells
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PROVIDER: PRJNA93955 | ENA |
REPOSITORIES: ENA
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Project description:Smad7 is a member of the TGF-B superfamily that plays a signigicant role in fate determination of hematopoietic stem cells. This experiment compares expression between megakaryotic and fibroblast cell lines that have been transduced with either Smad7 recombinant retroviral vector or retroviral vector alone. Keywords: other
2005-12-09 | GSE3771 | GEO
Project description:Smad7 is a member of the TGF-B superfamily that plays a signigicant role in fate determination of hematopoietic stem cells. This experiment compares expression between megakaryotic and fibroblast cell lines that have been transduced with either Smad7 recombinant retroviral vector or retroviral vector alone. Experiment Overall Design: this experiment include 4 samples and 30 replicates
2008-06-12 | E-GEOD-3771 | biostudies-arrayexpress
Project description:G0 marker-separation of dormant and active hematopoietic stem cells reveals dormancy regulation by basal cytoplasmic calcium
2019-12-19 | PXD012093 | JPOST Repository
Project description:The formation of hematopoietic cells relies on the chromatin remodeling activities of ISWI ATPase SMARCA5 (SNF2H) and its complexes. The Smarca5 null and conditional alleles have been used to study its functions in embryonic and organ development in mice. These mouse model phenotypes vary from embryonic lethality of constitutive knockout to less severe phenotypes observed in tissue-specific Smarca5 deletions, e.g., in the hematopoietic system. Here we show that, in a gene dosage-dependent manner, the hypomorphic allele of SMARCA5 (S5tg) can rescue not only the developmental arrest in hematopoiesis in the hCD2iCre model but also the lethal phenotypes associated with constitutive Smarca5 deletion or Vav1iCre-driven conditional knockout in hematopoietic progenitor cells. Interestingly, the latter model also provided evidence for the role of SMARCA5 expression level in hematopoietic stem cells, as the Vav1iCre S5tg animals accumulate stem and progenitor cells. Furthermore, their hematopoietic stem cells exhibited impaired lymphoid lineage entry and differentiation. This observation contrasts with the myeloid lineage which is developing without significant disturbances. Our findings indicate that animals with low expression of SMARCA5 exhibit normal embryonic development with altered lymphoid entry within the hematopoietic stem cell compartment.
2025-10-27 | PXD048865 | panorama
Project description:Induction of the inhibitory Smad, Smad7 serves as a negative feedback mechanism that restrains TGF-b-mediated actions in injured tissues. In inflammatory cells, Smad7 has been suggested to exert both pro-inflammatory actions attributed to inhibition of TGF-b-induced suppression of inflammation, and anti-inflammatory effects due to disruption of the TAK-1/NF-kB system. Myocardial infarction triggers a macrophage-driven inflammatory response that plays a central role in cardiac repair, but also contributes to adverse remodeling and fibrosis. We hypothesized that Smad7 upregulation in infarct macrophages may play a modulatory role in cardiac repair, by restraining effects of TGF-b. To test the hypothesis, we investigated the response of Myeloid cell-specific Smad7 knockout mice (MyS7KO) following myocardial infarction protocols, and we examined the in vitro effects of Smad7 in isolated macrophages. Smad7 was upregulated in a subset of infarct macrophages, peaking 7 days after infarction. Myeloid cell-specific Smad7 loss did not affect baseline macrophage gene expression and had no significant effects on homeostatic functions. Although RNA-seq analysis predicted that, in the absence of Smad7, infarct macrophages may have attenuated activation of inflammatory pathways and suppressed TREM1 signaling, myeloid cell-specific Smad7 loss had no significant effects on ventricular dysfunction, adverse remodeling, scar remodeling and collagen deposition after myocardial infarction. In isolated macrophages, TGF-b attenuated pro-inflammatory cytokine and chemokine expression, modulated synthesis of matrix remodeling genes, and had profound effects on macrophage profile, inducing genes associated with activation of sphingosine-1 phosphate and integrin signaling pathways, and inhibiting cholesterol biosynthesis genes. However, RNA-seq and PCR array experiments showed that Smad7 loss has minimal effects on TGF-b-mediated macrophage responses, restraining synthesis of only a small fraction of TGF-b-induced genes, such as Itga5, Olfml3 and Fabp7. Smad7 absence did not affect the anti-inflammatory actions of TGF-b in TNF-stimulated cells. In conclusion, our findings suggest a limited role for macrophage Smad7 in regulation of post-infarction inflammation and repair, and demonstrate that the anti-inflammatory effects of TGF-b in macrophages are not restrained by endogenous Smad7 induction.
2022-04-29 | GSE189450 | GEO
Project description:Induction of the inhibitory Smad, Smad7 serves as a negative feedback mechanism that restrains TGF-b-mediated actions in injured tissues. In inflammatory cells, Smad7 has been suggested to exert both pro-inflammatory actions attributed to inhibition of TGF-b-induced suppression of inflammation, and anti-inflammatory effects due to disruption of the TAK-1/NF-kB system. Myocardial infarction triggers a macrophage-driven inflammatory response that plays a central role in cardiac repair, but also contributes to adverse remodeling and fibrosis. We hypothesized that Smad7 upregulation in infarct macrophages may play a modulatory role in cardiac repair, by restraining effects of TGF-b. To test the hypothesis, we investigated the response of Myeloid cell-specific Smad7 knockout mice (MyS7KO) following myocardial infarction protocols, and we examined the in vitro effects of Smad7 in isolated macrophages. Smad7 was upregulated in a subset of infarct macrophages, peaking 7 days after infarction. Myeloid cell-specific Smad7 loss did not affect baseline macrophage gene expression and had no significant effects on homeostatic functions. Although RNA-seq analysis predicted that, in the absence of Smad7, infarct macrophages may have attenuated activation of inflammatory pathways and suppressed TREM1 signaling, myeloid cell-specific Smad7 loss had no significant effects on ventricular dysfunction, adverse remodeling, scar remodeling and collagen deposition after myocardial infarction. In isolated macrophages, TGF-b attenuated pro-inflammatory cytokine and chemokine expression, modulated synthesis of matrix remodeling genes, and had profound effects on macrophage profile, inducing genes associated with activation of sphingosine-1 phosphate and integrin signaling pathways, and inhibiting cholesterol biosynthesis genes. However, RNA-seq and PCR array experiments showed that Smad7 loss has minimal effects on TGF-b-mediated macrophage responses, restraining synthesis of only a small fraction of TGF-b-induced genes, such as Itga5, Olfml3 and Fabp7. Smad7 absence did not affect the anti-inflammatory actions of TGF-b in TNF-stimulated cells. In conclusion, our findings suggest a limited role for macrophage Smad7 in regulation of post-infarction inflammation and repair, and demonstrate that the anti-inflammatory effects of TGF-b in macrophages are not restrained by endogenous Smad7 induction.
2022-04-29 | GSE187701 | GEO
Project description:Metabolomic data of conditioned media derived from culturing hematopoietic stem cells.
2025-02-14 | MSV000097113 | GNPS
Project description:The role of CD74 in Hematopoietic Stem Cells
| PRJNA687020 | ENA
Project description:Autophagy engaging and non-engaging hematopoietic stem cells
| PRJNA958188 | ENA
Project description:Cardiomyocytes are the major effectors of cardiac remodeling under pressure overload, undergoing hypertrophy and contractile dysfunction in response to sustained mechanical stress. These maladaptive changes are orchestrated by transforming growth factor beta (TGF-β), a key mediator of hypertrophic and profibrotic signaling. Smad7, an inhibitory Smad, negatively regulates TGF-β signaling, but its cardiomyocyte-specific role in pathological remodeling is unclear. We hypothesized that Smad7 acts as an endogenous inhibitor of cardiomyocyte dysfunction during pressure overload. To investigate this, we generated cardiomyocyte-specific Smad7 knockout (CMS7KO) mice and subjected them to transverse aortic constriction (TAC). Echocardiography, RNA-sequencing, histological, and molecular analyses were performed. Smad7 expression was upregulated in cardiomyocytes of TAC mouse hearts and in patients with non-ischemic cardiomyopathy. While baseline cardiac function was preserved in CMS7KO mice, TAC induced an increase in systolic and diastolic dysfunction, ventricular dilation, and hypertrophy compared to controls. Histological analysis revealed increased cardiomyocyte size and macrophage infiltration, without significant fibrosis. Transcriptomic profiling showed downregulation of contractile and sarcomeric genes. Cardiomyocyte-specific Smad7 loss enhanced TGF-β/Smad3 and ERBB2 signaling in vivo. In H9c2 cardiomyocyte-like cells, Smad7 knockdown increased TbR1 and Smad3 phosphorylation, confirming a direct inhibitory effect. These findings identify cardiomyocyte Smad7 as a critical regulator of pathological remodeling and a potential therapeutic target in heart failure.
2026-06-06 | GSE299451 | GEO