KLF2 may suppress chicken adipogenesis by enhancing the GATA2 transcription
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1292095 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Kruppel-like factor 2 (KLF2) acts as an essential modulator of adipogenesis; nevertheless, the exact molecular pathways governing its role remain uncharacterized. This investigation characterized the expression profile of KLF2 in human adipose tissue and elucidated the mechanisms by which KLF2 modulates adipogenesis in avian models. The KLF2 mRNA expression in human adipose tissues was substantial and exhibited significant heterogeneity influenced by gender and anatomical location, suggesting that KLF2 regulated adipose tissue functionality. In chicken preadipocytes ICP1, the KLF2 protein increased at the first 24 h of oleate-induced adipogenic differentiation and subsequently decreased over time. KLF2 facilitated the cellular proliferation of ICP1 cells (P<0.05). Moreover, KLF2 overexpression inhibited differentiation of chicken preadipocytes ICP1 (P<0.05). KLF2 also increased the density of mitochondria and mitochondrial cristae in ICP1 cells. RNA seq and luciferase reporter assays demonstrated that KLF2 suppressed the expression of genes in PPAR signaling pathway in ICP1 cells. Additionally, KLF2 interacted with the promoter region of chicken GATA2 and upregulated GATA2 transcription in ICP1 cells. In summary, KLF2 potentially influences the PPAR signaling cascade, mitochondrial bioenergetics, and GATA2 gene expression to enhance the proliferation of avian preadipocytes while inhibiting their differentiation.
2025-07-17 | GSE302747 | GEO
Project description:GATA2 expression in endometrial serous carcinoma cells correlates with patient outcome. Depletion of GATA2 in patient-derived endometrial serous carcinoma cell lines correlates with invasive potential. As GATA2 is a transcription factor, we hypothesize that GATA2-dependent target genes normally suppress invasion in endometrial serous carcinoma.
2025-03-06 | GSE264610 | GEO
Project description:Our previous single-cell RNA sequencing study in the adult human heart revealed that cardiomyocytes from both the atrium and ventricle display high activities of Krüppel-like factor 2 (KLF2) regulons. However, the role of the transcription factor KLF2 in cardiomyocyte biology remains largely unexplored. We employed transverse aortic constriction surgery in male C57BL/6J mice to develop an in vivo model of cardiac hypertrophy, and generated different in vitro cardiac hypertrophy models in neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes. Our results demonstrated a significant reduction in KLF2 expression during the progression of cardiac hypertrophy. In vitro, KLF2 deficiency exacerbates cardiac hypertrophy and enhances hypertrophic reprogramming, while KLF2 overexpression attenuates cardiac hypertrophy and reverses hypertrophic transcriptome reprogramming. Mechanistically, combined RNA-seq and cleavage under targets & tagmentation (CUT&Tag) analysis revealed that KLF2 exerts its protective effects by directly regulating a set of genes associated with cardiac hypertrophy. In vivo, KLF2 overexpression specifically in cardiomyocytes effectively prevents TAC-induced cardiac hypertrophy in mice. Additionally, we found that simvastatin elevates KLF2 expression in cardiomyocytes, which subsequently alleviates cardiomyocyte hypertrophy. This study provides the first evidence that transcription factor KLF2 serves as a negative regulator of cardiac hypertrophy. Our findings highlight the therapeutic potential of enhancing KLF2 expression, particularly through simvastatin administration, as a promising strategy in the treatment of cardiac hypertrophy.
2025-01-01 | GSE283973 | GEO
Project description:As the most common vascular tumor during infancy, infantile hemangioma (IH) is clinically featured by a rapid proliferation phase of disorganized blood vessels and a subsequent spontaneous involution phase. Infantile hemangioma arises from a unique type of multipotent stem cells called hemangioma stem cells (HemSCs), which could differentiate into endothelial cells, pericytes and adipocytes in IH. However, the underlying mechanisms that regulate the cell fate determination of HemSCs are not well elucidated. Here, we identified KLF2 as a candidate transcription factor involved in the control of HemSCs differentiation. KLF2 was expressed in endothelial cells in proliferating IH and its expression diminished in adipocytes in involuting IH. KLF2 regualtes the proliferation, apopotosis and cell cycle progression in HemSCs. Moreover, KLF2 is a critical regulator in HemSCs that control their differentiation direction between endothelial cells and adipocytes. Knockdown of KLF2 inhibited the formation of blood vessels in vivo while accelerated the progress of adipogenesis. RNA-seq analysis suggested an induction of pro-adipogenic transcriptome in HemSCs upon KLF2 knockdown. Our data showed that KLF2 exhibited pleiotropic effects in regulating the biological behaviours of HemSCs, and was involved in the progression and involution of IH via determining the cell fate of HemSCs.
2024-08-01 | GSE239352 | GEO
Project description:Using a bioinformatics algorithm, we screened in silico 2,650 clinically relevant drugs for a potential GATA2 inhibitor. We identified the vasodilator Dilazep as a potential GATA2 inhibitor. Dilazep exerted anticancer activity across a broad panel of PC cell lines. Global gene expression analysis revealed that dilazep suppressed the GATA2, AR, and cMyc transcriptional programs, including under CRPC conditions. We also documented suppression of cell cycle programs and decreased expression of oncogenic drivers, such as FOXM1, CENPF, EZH2, UBE2C, RRM2, as well as several mediators of metastasis, DNA damage repair and stemness. We provide, based on global gene expression analysis, proof-of-principle evidence that a small molecule can inhibit GATA2 in PC cells and can suppress its downstream AR, cMyc, and other cancer-driving effectors. We propose that GATA2 can be a therapeutic target in CRPC.
2025-03-15 | GSE147215 | GEO
Project description:Using a bioinformatics algorithm, we screened in silico 2,650 clinically relevant drugs for a potential GATA2 inhibitor. We identified the vasodilator Dilazep as a potential GATA2 inhibitor. Dilazep exerted anticancer activity across a broad panel of PC cell lines. Global gene expression analysis revealed that dilazep suppressed the GATA2, AR, and cMyc transcriptional programs, including under CRPC conditions. We also documented suppression of cell cycle programs and decreased expression of oncogenic drivers, such as FOXM1, CENPF, EZH2, UBE2C, RRM2, as well as several mediators of metastasis, DNA damage repair and stemness. We provide, based on global gene expression analysis, proof-of-principle evidence that a small molecule can inhibit GATA2 in PC cells and can suppress its downstream AR, cMyc, and other cancer-driving effectors. We propose that GATA2 can be a therapeutic target in CRPC.
2025-03-15 | GSE147175 | GEO
Project description:Estrogen and obesity synergistically suppress Protein S via HIF1α, enhancing thrombotic potential
| PRJNA1203253 | ENA
Project description:The self-renewing pluripotent state was first captured in mouse embryonic stem cells (mESCs) over two decades ago. The standard condition requires the presence of serum and LIF, which provide growth promoting signals for cell expansion. However, there are pro-differentiation signals which destabilize the undifferentiated state of mESCs. The dual inhibition (2i) of the pro-differentiation Mek/Erk and Gsk3/Tcf3 pathways in mESCs is sufficient to establish an enhanced pluripotent “ground state” which bears features resembling the pre-implantation mouse epiblast. Gsk3 inhibition alleviates the repression of Esrrb, a transcription factor that can substitute for Nanog function in mESCs. The molecular mechanism that is mediated by Mek inhibition is however not clear. In this study, we investigate the pathway through which Mek inhibition operates to maintain ground state pluripotency. We have found that in mESCs, Kruppel-like factor 2 (Klf2) is a protein target of the Mek/Erk pathway; and that Klf2 protein is phosphorylated by Erk2 and subsequently degraded through the proteosome. It is therefore by Mek-inhibition through PD0325901 or 2i that enables the stabilization and accumulation of Klf2 to sustain ground state pluripotency. Importantly, we found that Klf2-null mESCs, while viable under LIF/Serum conditions, cannot be maintained and eventually gradually die within a few passages. Our result thus demonstrates that Klf2 is an essential factor of ground state pluripotency. Collectively, our study defines the Mek/Klf2 axis that cooperates with the Gsk3/Esrrb pathway in mediating ground state pluripotency.
2014-06-04 | E-MTAB-2366 | biostudies-arrayexpress