LEPR lineage cells in CAF development and the regulatory role of the KLF1 transcription factor in CRC CAF function
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE218869 | GEO | 2023/12/31
REPOSITORIES: GEO
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Project description:LEPR lineage cells in CAF development and the regulatory role of the KLF1 transcription factor in CRC CAF function
| PRJNA906050 | ENA
Project description:In this project we did a proteomic analysis from iPSCs-derived macrophages with the activation of thranscription factor KLF1, upon tamoxifen induction. These macrophages are a model for the study of the erythroid island (EI) niche in adult hematopoietic tissues, such as bone marrow and spleen. We wanted to assess the upregulated proteins in macrophages upon KLF1 activation to further study the interactions between macrophages and erythroid cells whithin the EI niche.
2024-06-23 | PXD050357 | Pride
Project description:Krueppel-like factor 1 (KLF1) is a major transcription factor, which regulates the γ-globin to β-globin gene switch during erythropoiesis. The goal of this study was to investigate genome-wide transcriptome expression pattern in the presence of KLF1 knockdown to discover targets of KLF1 regulation involved in γ-globin silencing. To achieve KLF1 gene silencing, we stably transfected human primary erythroid cells generated from CD34+ cells, with a short hairpin lentiviral vector carrying a shKLF1 (short hairpin RNA for KLF1 loop) and a puromycin resistance gene. A set of three shKLF1 were designed uusing siDesign Center (Dharmacon) with the designations: 1) shKLF1-1, located in zinc finger at 3'-terminal; 1) shKLF1-2 located in Transcription Factor II H, and 3) shKLF1-3 located in 5’-terminal without a function region. After lentiviral packaging and transduction into CD34+ cells, each expression virus with encoding GFP, puromycin resistance fragment, and a loop consists of the KLF1 knock-down domain. The three shKLF1 vectors (shKLF1-1, shKLF1-2, shKLF1-3), along with scrambled control (shScr) was used to transduce human adult CD34+ stem cells isolated from peripheral blood of healthy adults. The cells were grown in one-phase liquid culture system as previously published by our group (Li B et al. Characterization of the transcriptome profiles related to globin gene switching during in vitro erythroid maturation. BMC Genomics. 2012; 13:153). At day-15 in the 28-day culture period, by real-time PCR and Western blot analysis we found KLF1 gene silencing mainly for shKLF-1 and shKLF-2; however, we isolated total RNA from the three stable lines for RNA-seq analysis.
2021-05-12 | GSE174276 | GEO
Project description:Leptin receptors (Lepr) are expressed by various types of stem cells including mesenchymal stem cells, hematopoietic stem cells, embryonic stem cells, and induced pluripotent stem cells. Leptin/lepr signaling is also a central regulator of metabolism. However, the role of Lepr in pluripotency, metabolic disease progression and growth development is still controversial and poorly understood. In the present study, we explored the Lepr function in disease progression, pluripotency and metabolism using day 14.5 mouse embryonic fibroblasts (MEFs) and their reprogrammed induced pluripotent stem cells (iPSCs) as model system. We successfully reprogrammed mouse embryonic fibroblasts into iPSCs from control and db/db (Lepr deficient) mice. Using a global quantitative proteomic approach, we identified key pathways regulating pluripotency, metabolic homeostasis and protein synthesis during fetal growth and development. The Lepr MEFs show abnormal metabolic abnormalities and mitochondrial dysfunction as compared to control MEFs, while Lepr iPSCs show upregulated elongated factor 4 e (eIF4e) protein synthesis pathway and altered Oct4 and Stat3 pathways which are involved in normal fetal growth development. Furthermore, chip analysis revealed that higher Stat3 binding on the promoter of eIF4e in Lepr iPSCs leads to higher protein synthesis in these cell types as compared to control iPSCs. Finally, point mutation corrected Lepr iPSCs using CRISPR/Cas9 gene editing method showed recovered pluripotency, metabolic and protein synthesis pathways. In conclusion, we have shown that Lepr signaling is involved in the regulation of the metabolic properties and key developmental pathways in MEFs and stemness of pluripotent stem cells. Disruption of Lepr signaling has been shown to involve in the pathophysiology of various diseases including obesity and diabetes. The generated MEFs and iPSCs in this present study provide valuable tools to explore the role of Lepr in the progression of obesity, diabetes and metabolic abnormalities, and to find the putative targets of Lepr signaling during the development of these diseases.
2021-09-09 | PXD020959 | Pride
Project description:KLF1 (EKLF) regulates a diverse suite of genes to direct erythroid cell differentiation from bi-potent progenitors. To determine the local cis-regulatory contexts and transcription factor networks in which KLF1 operates, we performed KLF1 ChIP-seq in the mouse. We found at least 945 sites in the genome of E14.5 fetal liver erythroid cells which are occupied by endogenous KLF1. Many of these recovered sites reside in erythroid gene promoters such as β-globin, but the majority are distant to any known gene. Our data suggests KLF1 directly regulates most aspects of terminal erythroid differentiation including production of α and β-globin protein chains, heme biosynthesis, co-ordination of proliferation and anti-apoptotic pathways, and construction of the red cell membrane and cytoskeleton by functioning primarily as a transcriptional activator. Additionally, we suggest new mechanisms for KLF1 co-operation with other transcription factors, in particular the erythroid transcription factor GATA1, to maintain homeostasis in the erythroid compartment. Examination of KLF1 occupancy in primary erythroid cells. KLF1-ChIP and input samples were run on AB SOLiD Systems 2.0 and 3.0. The genomic alignment files (*sorted.txt) and peak file (*bed) contain the combined System 2.0 and 3.0 data.
2010-04-08 | E-GEOD-20478 | biostudies-arrayexpress
Project description:Congenital dyserythropoietic anaemia (CDA) type IV has been associated with an amino acid substitution, Glu325Lys (E325K), in the transcription factor KLF1. Patients with CDA type IV present with a range of symptoms, including the persistence of nucleated red blood cells (RBCs) in the peripheral blood which reflects the known role for KLF1 within the erythroid cell lineage. The final stages of RBCs maturation and enucleation take place within the erythroblastic island (EBI) niche in close association with EBI macrophages. It is not known whether the detrimental effects of the E325K mutation in KLF1 are restricted to the erythroid lineage or whether deficiencies in macrophages associated with their niche also contribute to the disease pathology. To address this question, we generated iPSC lines genetically modified to express a KLF1-E325K-ERT2 protein that could be activated with 4OH-tamoxifen. We performed bulk RNA-sequencing on macrophages generated from these iPSCs, macrophages generated from one KLF1-E325K-ERT2 iPSC line (iCDA4.1) was compared to macrophages generated from one inducible KLF1-WT-ERT2 (K2) iPSC line which was derived from the same parental iPSCs (SFCi55) as the KLF1-E325K-ERT2 line.
2023-03-31 | GSE228537 | GEO
Project description:RNA-sequencing comparing activation of wild-type transcription factor KLF1 with mutant KLF1 (KLF1-325K) in iPSC-derived macrophages.
| PRJNA950312 | ENA
Project description:KLF1 (EKLF) regulates a diverse suite of genes to direct erythroid cell differentiation from bi-potent progenitors. To determine the local cis-regulatory contexts and transcription factor networks in which KLF1 operates, we performed KLF1 ChIP-seq in the mouse. We found at least 945 sites in the genome of E14.5 fetal liver erythroid cells which are occupied by endogenous KLF1. Many of these recovered sites reside in erythroid gene promoters such as β-globin, but the majority are distant to any known gene. Our data suggests KLF1 directly regulates most aspects of terminal erythroid differentiation including production of α and β-globin protein chains, heme biosynthesis, co-ordination of proliferation and anti-apoptotic pathways, and construction of the red cell membrane and cytoskeleton by functioning primarily as a transcriptional activator. Additionally, we suggest new mechanisms for KLF1 co-operation with other transcription factors, in particular the erythroid transcription factor GATA1, to maintain homeostasis in the erythroid compartment.
2010-04-08 | GSE20478 | GEO
Project description:Leptin receptor (LEPR) identifies a subpopulation of hematopoietic stem cells (HSCs) with high repopulating potential. In this study, we demonstrated that LEPR-expressing HSCs while exhibiting significantly higher engrafting potential and self-renewing capacity in young mice showed early age-associated decline in these functions as compared to the LEPR- HSCs. LEPR+ HSCs have transcriptomic profiles significantly different from LEPR- HSCs in young mouse bone marrow, but middle-aged HSCs do not have distinct transcriptomic profiles based on LEPR status. The age-related phenotypes were associated with a proinflammatory transcriptomic profile at baseline in young LEPR+ HSCs, which was further exacerbated by age. In contrast, LEPR- HSCs did not show age-associated functional impairment at the ages tested. This suggested that subsets of HSCs are susceptible to age-related decline in function at varying ages and that LEPR+ HSCs are a potential target for early cellular therapeutic interventions in delaying the detrimental effects of aging in hematopoiesis.
2023-02-18 | GSE221126 | GEO
Project description:To study the regulation of Lepr on transcriptome in WT and Lepr KO AMs under resting state and after LPS stimulation, Lepr-sufficient (Lepr+/+, Lyz2-Cre) and Lepr-deficient (Leprfl/fl, Lyz2-Cre) alveolar macrophages (AMs) were isolated by collecting BALF. Lipopolysaccharide (LPS) was added in vitro for 1h or cells were left untreated. Total RNA was extracted for deep sequencing. Gene expression in WT and Lepr KO cells were analyzed.
2022-07-20 | GSE185218 | GEO