The first site exhibiting hematopoietic activity in mammalian development is the yolk sac blood island, which originates from the hemangioblast. Here we performed differentiation assays, as well as genome-wide molecular and functional studies in BL-CFCs to gain insight into the function of the essential Ldb1 factor in early primitive hematopoietic development. We show that the previously reported lack of yolk sac hematopoiesis and vascular development in Ldb1-/- mouse result from a decreased number of hemangioblasts and a block in their ability to differentiate into erythroid and endothelial progenitor cells. Transcriptome analysis and correlation with the genome wide binding pattern of Ldb1 in hemangioblasts revealed a number of direct target genes and pathways misregulated in the absence of Ldb1. The regulation of essential developmental factors by Ldb1 defines it as an upstream transcriptional regulator of hematopoietic/endothelial development. We show the complex interplay that exists between transcription factors and signaling pathways during the very early stages of hematopoietic/endothelial development and the specific signalling occurring in hemangioblasts in contrast to more advanced hematopoietic developmental stages. Finally, by revealing novel genes and pathways, not previously associated with early development, our study provides novel candidate targets to manipulate the differentiation of hematopoietic and/or endothelial cells.
Genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis.
Specimen part
View SamplesIKKbeta is a subunit of the IkB kinase (IKK) complex required for NF-kB activation in response to pro-inflammatory signals. NF-kB regulates the expression of many genes involved in inflammation, immunity and apoptosis, and also controls cell proliferation and differentiation in different tissues; however, its function in skin physiopathology remains controversial. We here report the alterations caused by increased IKKbeta activity in basal cells of the skin of transgenic mice.
IKKbeta leads to an inflammatory skin disease resembling interface dermatitis.
Sex, Age, Specimen part
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The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Specimen part, Treatment, Time
View SamplesMice were treated with either 100mg/kg baclofen or 0.5% methylcellulose alone by oral gavage for 1 or 5 days.
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Specimen part, Treatment, Time
View SamplesMice were dosed with 2-BE (900mg/kg) or vehicle by oral gavage and sacrificied either after 4 hours of a single dose or after 7 days of daily dosing.
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Specimen part, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dynamic regulatory network controlling TH17 cell differentiation.
Specimen part, Treatment
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