Bcl11a is a transcription factor known to regulate lymphoid and erythroid development. Recent bioinformatic analysis of global gene expression patterns has suggested a role for Bcl11a in the development of dendritic cell (DC) lineages. We tested this hypothesis by analyzing the development of DC and other lineages in Bcl11a(-/-) mice. We show that Bcl11a is required for expression of IL-7 receptor (IL-7R) and Flt3 in early hematopoietic progenitor cells. The loss of IL-7R(+) common lymphoid progenitors accounts for previously described lymphoid defects in Bcl11a(-/-) mice. In addition, we found severely decreased numbers of plasmacytoid dendritic cells (pDCs) in Bcl11a(-/-) fetal livers and in the bone marrow of Bcl11a(-/-) fetal liver chimeras. Moreover, Bcl11a(-/-) cells show severely impaired in vitro development of Flt3L-derived pDCs and classical DCs (cDCs). In contrast, we found normal in vitro development of DCs from Bcl11a(-/-) fetal liver cells treated with GM-CSF. These results suggest that the persistent cDC development observed in Bcl11a(-/-) fetal liver chimeras reflects derivation from a Bcl11a- and Flt3-independent pathway in vivo.
Bcl11a controls Flt3 expression in early hematopoietic progenitors and is required for pDC development in vivo.
Specimen part
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IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors.
Specimen part
View SamplesWhile most blood lineages are assumed to mature through a single cellular and developmental route downstream of hematopoietic stem cells (HSCs), dendritic cells (DCs) can be derived from both myeloid and lymphoid progenitors in vivo. To determine how distinct progenitors can generate similar downstream lineages, we examined the transcriptional changes that accompany loss of in vivo myeloid potential as common myeloid progenitors (CMPs) differentiate into common dendritic cell progenitors (CDPs), and as lymphoid-primed multipotent progenitors (LMPPs) differentiate into all lymphoid progenitors (ALPs). Microarray studies revealed that Interferon regulatory factor 8 (IRF-8) expression increased during each of these transitions. Competitive reconstitutions using Irf8-/- bone marrow demonstrated cell-intrinsic defects in the formation of CDPs and all splenic dendritic cell subsets. Irf8-/- CMPs and, unexpectedly, Irf8-/- ALPs produced more neutrophils in vivo than their wild type counterparts at the expense of DCs. Retroviral expression of IRF-8 in multiple progenitors led to reduced neutrophil production and increased numbers of DCs, even in the granulocyte-macrophage progenitor (GMP), which does not normally possess conventional DC potential. These data suggest that IRF-8 represses a neutrophil module of development and promotes convergent DC development from multiple lymphoid and myeloid progenitors autonomously of cellular context.
IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dual actions of Meis1 inhibit erythroid progenitor development and sustain general hematopoietic cell proliferation.
Specimen part, Treatment
View SamplesThe homeodomain protein Meis1 is essential for definitive hematopoiesis and vascular patterning in the mouse embryo. Meis2, another member of the same family, shares 82% protein identities with Meis1. Our present study suggested Meis2 exerts two distinguishable effects in differentiating ES cells. First, it increases the numbers of hematopoietic progenitors and extends their persistence in culture. Second, Meis2 skews hematopoietic differentiation by suppressing erythroid while enhancing megakaryocytic progenitor differentiation. To identify the underlying transcriptional bases of these actions, we carried out microarray analysis to compare the various populations of cells developing in ES differentiation cultures in the presence and absence of Meis2 induction.
Dual actions of Meis1 inhibit erythroid progenitor development and sustain general hematopoietic cell proliferation.
Specimen part, Treatment
View SamplesThe homeodomain protein Meis1 is essential for definitive hematopoiesis and vascular patterning in the mouse embryo. Our present study suggested it exerts two distinguishable effects in differentiating ES cells. First, it increases the numbers of hematopoietic progenitors and extends their persistence in culture. Second, Meis1 skews hematopoietic differentiation by suppressing erythroid while enhancing megakaryocytic progenitor differentiation. To identify the underlying transcriptional bases of these actions, we carried out microarray analysis to compare the various populations of cells developing in ES differentiation cultures in the presence and absence of Meis1 induction.
Dual actions of Meis1 inhibit erythroid progenitor development and sustain general hematopoietic cell proliferation.
Specimen part, Treatment
View SamplesPreviously, we reported that the transcription factor Mesp1 promotes the cell fates of cardiomyocytes, smooth muscle, and vascular endothelium. Recently, hematopoietic stem cells (HSCs) were shown to derive from hemogenic endothelium. Since Mesp1 regulates development of endothelium, it potentially could influence gene expression related to hematopoietic development.
Dual actions of Meis1 inhibit erythroid progenitor development and sustain general hematopoietic cell proliferation.
Specimen part, Treatment
View SamplesCiita has been suggested to control the expression of a number of genes based on ChIP-Seq or reporter anaysis but in vivo regulation beyong MHC class II has largely not been confirmed. We crossed Ciita knock out mice to Zbtb46 GFP knock-in knock out mice to identify classical dendritic cells in vivo in a Ciita deficient background.
Revisiting the specificity of the MHC class II transactivator CIITA in classical murine dendritic cells in vivo.
Specimen part
View SamplesRunx/Cbfb heterodimers play important roles in the development of hematopoietic cells in mouse embryos and adults. In order to identify genes that are regulated by Runx/Cbfb, we purified Lin c-kit+ Sca1+ (LSK) cells and Lin c-kit+ Sca1 CD16/32+ (GMP) cells from Vav1-iCre x Cbfb(F/F) and Vav1-iCre x Cbfb(F/+) mice and profiled gene expression using microarray.
Runx1 and Cbfβ regulate the development of Flt3+ dendritic cell progenitors and restrict myeloproliferative disorder.
Specimen part
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