Wnt-4 signaling is critical for embryonic female sexual development. When Wnt-4 gene is deleted during embryonic development, the knock-out females present a partial sex reversal.
Identification of the genes regulated by Wnt-4, a critical signal for commitment of the ovary.
Specimen part
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The transcription factor Foxo1 controls central-memory CD8+ T cell responses to infection.
Specimen part
View SamplesWe used microarrays to detail the global programme of gene expression dependent upon Stat3 in regulatory T cells
CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner.
Sex, Specimen part
View SamplesGroup-2 innate lymphoid cells (ILC2) serve crucial function in allergy and asthma. Activated ILC2 rapidly proliferate and secret large amounts of type-2 cytokines, such as IL-5 and IL-13. Mechanisms underlying still remain ambiguous. Here we report that Myc is required for ILC2 proliferation and activation in allergic airway inflammation. Inhibition of Myc impair the ILC2 proliferation in vivo and prevented ILC2-mediated airway hyperresponsiveness in vivo.
A critical role for c-Myc in group 2 innate lymphoid cell activation.
Genotype, Cell line
View SamplesCold triggers VEGF dependent but hypoxia independent angiogenesis in adipose tissues and anti-VEGF agents modulate adipose metabolism
Hypoxia-independent angiogenesis in adipose tissues during cold acclimation.
Sex
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Novel Foxo1-dependent transcriptional programs control T(reg) cell function.
Specimen part
View SamplesCytosine methylation is an epigenetic mark usually associated with gene repression. Despite a requirement for de novo DNA methylation for differentiation of embryonic stem cells, its role in somatic stem cells is unknown. Using conditional ablation, we show that loss of either, or both, Dnmt3a or Dnmt3b, progressively impedes hematopoietic stem cell (HSC) differentiation during serial in vivo passage. Concomitantly, HSC self-renewal is immensely augmented in absence of either Dnmt3, particularly Dnmt3a. Dnmt3-KO HSCs show upregulation of HSC multipotency genes and downregulation of early differentiation factors, and the differentiated progeny of Dnmt3-KO HSCs exhibit hypomethylation and incomplete repression of HSC-specific genes. HSCs lacking Dnmt3a manifest hyper-methylation of CpG islands and hypo-methylation of genes which are highly correlated with human hematologic malignancies. These data establish that aberrant DNA methylation has direct pathologic consequences for somatic stem cell development, leading to inefficient differentiation and maintenance of a self-renewal program.
Dnmt3a is essential for hematopoietic stem cell differentiation.
Sex, Specimen part
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Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.
Specimen part, Cell line
View SamplesIkaros family DNA binding proteins are critical regulators of B cell development. To identify Ikaros-regulated genes in pre-B cells we performed gene expression studies at enhanced temporal resolution.
Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.
Specimen part, Cell line
View SamplesProgressive tissue fibrosis is a major cause of morbidity, and idiopathic pulmonary fibrosis (IPF) is a terminal illness characterized by unremitting matrix deposition in the lung with very limited choice of therapies. The imcomplete understanding of the mechanisms of progressive fibrosis curbs the progress in therapeutics development. Of which, the origin of fibrotic fibroblasts has been poorly defined during the pathogenesis of tissue fibrosis. Here, we fate-mapped a early embryonic transcription factor T-box gene 4 (Tbx4)-derived mesenchymal progenitors in injured adult lung and found that Tbx4+ lineage cells are the major source of myofibroblasts. The ablation of Tbx4+ cells or disruption of Tbx4 signaling attenuated lung fibrosis in bleomycin injury model in mice in vivo. Furthermore, Tbx4+ fibroblasts are more invasive and the regulation of fibroblast invasiveness by Tbx4 is through mediating hyaluronan synthase 2 (HAS2). This study identified a major mesenchymal transcription factor driving the development of fibrotic fibroblasts during lung fibrosis. Understanding the origin, signaling, and functions of these fibroblasts would prove pivotal in the development of therapeutics for patients with progressive fibrotic diseases.
Transcription factor TBX4 regulates myofibroblast accumulation and lung fibrosis.
Specimen part
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