Search results for "transcription factor"

NANOG Plays a Hierarchical Role in the Transcription Network Regulating the Pluripotency and Plasticity of Adipose Tissue-Derived Stem Cells

2017

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self-renewal potential and differentiation capacity. Our aim was to study the different expression of the embryonic stem cell markers NANOG (homeobox protein NANOG), SOX2 (SRY (sex determining region Y)-box 2) and OCT4 (octamer-binding transcription factor 4) and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting pat…

Identifying Host Molecular Features Strongly Linked With Responses to Huanglongbing Disease in Citrus Leaves

2018

© 2018 Balan, Ibáñez, Dandekar, Caruso and Martinelli. A bioinformatic analysis of previously published RNA-Seq studies on Huanglongbing (HLB) response and tolerance in leaf tissues was performed. The aim was to identify genes commonly modulated between studies and genes, pathways and gene set categories strongly associated with this devastating Citrus disease. Bioinformatic analysis of expression data of four datasets present in NCBI provided 46–68 million reads with an alignment percentage of 72.95–86.76%. Only 16 HLB-regulated genes were commonly identified between the three leaf datasets. Among them were key genes encoding proteins involved in cell wall modification such as CESA8, pecti…

Donor interleukin-22 and host type I interferon signaling pathway participate in intestinal graft-versus-host disease via STAT1 activation and CXCL10.

2014

Acute graft-versus-host disease (aGVHD) remains a major complication following allogeneic hematopoietic cell transplantation, limiting the success of this therapy. We previously reported that interleukin-22 (IL-22) participates to aGVHD development, but the underlying mechanisms of its contribution remain poorly understood. In this study, we analyzed the mechanism of the pathological function of IL-22 in intestinal aGVHD. Ex-vivo colon culture experiments indicated that IL-22 was able to induce Th1-like inflammation via signal transducer and activator of transcription factor-1 (STAT1) and CXCL10 induction in the presence of type I interferon (IFN). To evaluate a potential synergy between IL…

2020

β-thalassemia major (β-TM) is an inherited hemoglobinopathy caused by a quantitative defect in the synthesis of β-globin chains of hemoglobin, leading to the accumulation of free a-globin chains that aggregate and cause ineffective erythropoiesis. We have previously demonstrated that terminal erythroid maturation requires a transient activation of caspase-3 and that the chaperone Heat Shock Protein 70 (HSP70) accumulates in the nucleus to protect GATA-1 transcription factor from caspase-3 cleavage. This nuclear accumulation of HSP70 is inhibited in human β-TM erythroblasts due to HSP70 sequestration in the cytoplasm by free a-globin chains, resulting in maturation arrest and apoptosis. Like…

An essential role for the IL-2 receptor in Treg cell function

2016

Regulatory T cells (Treg cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg cell lineage-specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of Treg cells. Using genetic gain- and loss-of-function approaches, we found that capture of IL-2 was dispensable for the control of CD4+ T cells but was important …

The Role of JAK/STAT Molecular Pathway in Vascular Remodeling Associated with Pulmonary Hypertension

2021

Pulmonary hypertension is defined as a group of diseases characterized by a progressive increase in pulmonary vascular resistance (PVR), which leads to right ventricular failure and premature death. There are multiple clinical manifestations that can be grouped into five different types. Pulmonary artery remodeling is a common feature in pulmonary hypertension (PH) characterized by endothelial dysfunction and smooth muscle pulmonary artery cell proliferation. The current treatments for PH are limited to vasodilatory agents that do not stop the progression of the disease. Therefore, there is a need for new agents that inhibit pulmonary artery remodeling targeting the main genetic, molecular,…

Aryl Hydrocarbon Receptor in Keratinocytes Is Essential for Murine Skin Barrier Integrity.

2016

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in adaptive cell functions, and it is highly active in the epidermis. AhR ligands can accelerate keratinocyte differentiation, but the precise role of AhR in the skin barrier is unknown. Our study showed that transepidermal water loss, a parameter of skin barrier integrity, is high in AhR-deficient mice. Experiments with conditionally AhR-deficient mouse lines identified keratinocytes as the primary cell population responsible for high transepidermal water loss. Electron microscopy showed weaker intercellular connectivity in the epidermis of keratinocytes in AhR-knockout mice, and gene expression analysi…

Selective AhR knockout in langerin-expressing cells abates Langerhans cells and polarizes Th2/Tr1 in epicutaneous protein sensitization

2020

The aryl hydrocarbon receptor (AhR) represents an environmental sensor regulating immune responses. In the skin, AhR is expressed in several cell types, including keratinocytes, epidermal Langerhans cells (LC), and dermal dendritic cells (DC). The mechanisms how AhR activates or inhibits cutaneous immune responses remain controversial, owing to differences in the cell-specific functions of AhR and the different activating ligands. Therefore, we sought to investigate the role of AhR in LC and langerin(+) and negative DC in the skin. To this aim, we generated Langerin-specific and CD11c-specific knockout ((−/−)) mice lacking AhR, respectively, in LC and Langerin(+) dermal DC and in all CD11c(…

Development of the GABAergic and glutamatergic neurons of the lateral hypothalamus.

2021

In the last few years we assist to an unexpected deluge of genomic data on hypothalamic development and structure. Perhaps most surprisingly, the Lateral Zone has received much attention too. The new information focuses first of all on transcriptional heterogeneity. Many already known and a number of hitherto unknown lateral hypothalamic neurons have been described to an enormous degree of detail. Maybe the most surprising novel discoveries are two: First, some restricted regions of the embryonic forebrain neuroepithelium generate specific LHA neurons, either GABAergic or glutamatergic. Second, evidence is mounting that supports the existence of numerous kinds of "bilingual" lateral hypotha…

Nuclear Translocation of RELB Is Increased in Diseased Human Liver and Promotes Ductular Reaction and Biliary Fibrosis in Mice.

2019

Background & Aims Cholangiocyte proliferation and ductular reaction contribute to the onset and progression of liver diseases. Little is known about the role of the transcription factor nuclear factor-κB (NF-κB) in this process. We investigated the activities of the RELB proto-oncogene NF-κB subunit in human cholangiocytes and in mouse models of liver disease characterized by a ductular reaction. Methods We obtained liver tissue samples from patients with primary sclerosing cholangitis, primary biliary cholangitis, hepatitis B or C virus infection, autoimmune hepatitis, alcoholic liver disease, or without these diseases (controls) from a tissue bank in Germany. Tissues were analyzed by immu…