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Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Hoxb8-FL RNA-Seq]

ABSTRACT: Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Hoxb8-FL RNA-Seq]

PROVIDER: PRJNA836605 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19148200_1.fastq.gz	Fastqsanger.gz
	SRR19148200_2.fastq.gz	Fastqsanger.gz
	SRR19148201_1.fastq.gz	Fastqsanger.gz
	SRR19148201_2.fastq.gz	Fastqsanger.gz
	SRR19148202_1.fastq.gz	Fastqsanger.gz

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Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Hoxb8-FL RNA-Seq]

Project description:The development of all dendritic cells (DCs) including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs) is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected this common Flt3L-driven pathway of DCs differentiation using CRISPR/Cas9-based dropout screening in a Flt3L-dependent progenitor cell line. Genome-wide screening identified multiple regulators of DC differentiation including the glycosylphosphatidylinositol transamidase complex and arginine methyltransferase Carm1, whose role was confirmed in vivo. It also showed that negative regulators of mTOR signaling, including the subunits of TSC and GATOR1 complexes, restricted progenitor growth but enabled DC differentiation, demonstrating that a TSC- and GATOR1-mediated shutdown of mTOR is required for the process. An orthogonal screen focused on transcriptional regulators showed that Trim33 (TIF-1g) is required for DC differentiation. Conditional targeting in vivo revealed an essential role of Trim33 in the development of all DCs, but not of monocytes or granulocytes. In particular, inducible deletion of Trim33 caused a rapid loss of all DC progenitors, pDCs and the cross-presenting cDC1 subset. The loss of Trim33 from DC progenitors caused spontaneous interferon and inflammatory response, aberrant induction of macrophage-specific genes, and failure to induce DC differentiation program. Collectively, these data elucidate common mechanisms that control Flt3L-driven differentiation of the entire DC lineage, and identify Trim33 as its essential regulator.

2024-04-12 | GSE202584 | GEO

Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Hoxb8-FL ATAC-Seq]

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Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Hoxb8-FL Brie sgRNA-Seq]

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Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Hoxb8-FL TF sgRNA-Seq]

Project description:The development of all dendritic cells (DCs) including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs) is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected this common Flt3L-driven pathway of DCs differentiation using CRISPR/Cas9-based dropout screening in a Flt3L dependent progenitor cell line. Genome-wide screening identified multiple regulators of DC differentiation including the glycosylphosphatidylinositol transamidase complex and arginine methyltransferase Carm1, whose role was confirmed in vivo. It also showed that negative regulators of mTOR signaling, including the subunits of TSC and GATOR1 complexes, restricted progenitor growth but enabled DC differentiation, demonstrating that a TSC- and GATOR1-mediated shutdown of mTOR is required for the process. An orthogonal screen focused on transcriptional regulators showed that Trim33 (TIF-1g) is required for DC differentiation. Conditional targeting in vivo revealed an essential role of Trim33 in the development of all DCs, but not of monocytes or granulocytes. In particular, inducible deletion of Trim33 caused a rapid loss of all DC progenitors, pDCs and the cross-presenting cDC1 subset. The loss of Trim33 from DC progenitors caused spontaneous interferon and inflammatory response, aberrant induction of macrophage-specific genes, and failure to induce DC differentiation program. Collectively, these data elucidate common mechanisms that control Flt3L-driven differentiation of the entire DC lineage, and identify Trim33 as its essential regulator.

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Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Hoxb8-FL ATAC-Seq]

Project description:Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Hoxb8-FL ATAC-Seq]

| PRJNA836606 | ENA

Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Hoxb8-FL Brie sgRNA-Seq]

Project description:Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Hoxb8-FL Brie sgRNA-Seq]

| PRJNA837860 | ENA

Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Hoxb8-FL TF sgRNA-Seq]

Project description:Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Hoxb8-FL TF sgRNA-Seq]

| PRJNA1081403 | ENA

Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Trim33 RNA-Seq]

Project description:The development of all dendritic cells (DCs) including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs) is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected this common Flt3L-driven pathway of DCs differentiation using CRISPR/Cas9-based dropout screening in a Flt3L dependent progenitor cell line. Genome-wide screening identified multiple regulators of DC differentiation including the glycosylphosphatidylinositol transamidase complex and arginine methyltransferase Carm1, whose role was confirmed in vivo. It also showed that negative regulators of mTOR signaling, including the subunits of TSC and GATOR1 complexes, restricted progenitor growth but enabled DC differentiation, demonstrating that a TSC- and GATOR1-mediated shutdown of mTOR is required for the process. An orthogonal screen focused on transcriptional regulators showed that Trim33 (TIF-1g) is required for DC differentiation. Conditional targeting in vivo revealed an essential role of Trim33 in the development of all DCs, but not of monocytes or granulocytes. In particular, inducible deletion of Trim33 caused a rapid loss of all DC progenitors, pDCs and the cross-presenting cDC1 subset. The loss of Trim33 from DC progenitors caused spontaneous interferon and inflammatory response, aberrant induction of macrophage-specific genes, and failure to induce DC differentiation program. Collectively, these data elucidate common mechanisms that control Flt3L-driven differentiation of the entire DC lineage, and identify Trim33 as its essential regulator.

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Generation of hematopoietic progenitor cell lines with myeloid and lymphoid potential using a conditional form of Hoxb8

Project description:Investigation of immune cell differentiation and function is limited by shortcomings of suitable and scalable experimental systems. Although forced expression of certain Hox genes allows immortalization of hematopoietic progenitor cells, their differentiation potential is limited to select myeloid lineages. Here we show that an estrogen-regulated form of Hoxb8 that is retrovirally delivered into bone marrow cells can be used along with FLT3 ligand to conditionally immortalize early hematopoietic progenitor cells (Hoxb8-FL). Hoxb8-FL cells have lost self-renewal capacity and the ability to adopt megakaryocyte/ erythroid lineage fates, but sustain myeloid and lymphoid differentiation potential. Hoxb8-FL cells differentiate in vitro and in vivo into different myeloid and lymphoid cell types, including macrophages, granulocytes, dendritic cells and B- and T-lymphocytes, which are phenotypically and functionally indistinguishable from their primary counterparts. Given the simplicity to generate Hoxb8-FL cells and their unlimited proliferative capacity, this system provides unique opportunities to investigate cell differentiation and immune cell functions. Hoxb8 expressing immortalized cells

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Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Trim33 RNA-Seq]

Project description:Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Trim33 RNA-Seq]

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