Next Generation Sequencing of Wild Type and Zeb1-/- CLP and HSCs
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ABSTRACT:
PROVIDER: PRJNA643566 | ENA |
REPOSITORIES: ENA
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Project description:Zeb1, a zinc finger E-box binding homeobox epithelial-mesenchymal (EMT) transcription factor, confers properties of ‘stemness’, such as self-renewal, in cancer. Yet little is known about the function of Zeb1 in adult stem cells. Here, we used the hematopoietic system, as a well-established paradigm of stem cell biology, to evaluate Zeb1 mediated regulation of adult stem cells. We employed a conditional genetic approach using the Mx1-Cre system to specifically knockout (KO) Zeb1 in adult hematopoietic stem cells (HSCs) and their downstream progeny. Acute genetic deletion of Zeb1 led to rapid onset thymic atrophy and apoptosis driven loss of thymocytes and T cells. A profound cell-autonomous self-renewal defect and multi-lineage differentiation block was observed in Zeb1 KO HSCs. Loss of Zeb1 in HSCs activated transcriptional programs of deregulated HSC maintenance and multi-lineage differentiation genes, and of cell polarity, consisting of cytoskeleton, lipid metabolism/lipid membrane and cell adhesion related genes. Notably, Epithelial cell adhesion molecule (EpCAM) expression was prodigiously upregulated in Zeb1 KO HSCs, which correlated with their enhanced cell survival capacity and diminished differentiation in transplantation. Thus, Zeb1 acts as a crucial transcriptional regulator in hematopoiesis, co-ordinating HSC self-renewal and multi-lineage differentiation fates, in part, via EpCAM repression.
2020-07-02 | GSE153662 | GEO
Project description:Next Generation Sequencing of Wild Type and Zeb1-/- CLP
| PRJNA643569 | ENA
Project description:Zeb1, a zinc finger E-box binding homeobox epithelial-mesenchymal (EMT) transcription factor, confers properties of ‘stemness’, such as self-renewal, in cancer. Yet little is known about the function of Zeb1 in adult stem cells. Here, we used the hematopoietic system, as a well-established paradigm of stem cell biology, to evaluate Zeb1 mediated regulation of adult stem cells. We employed a conditional genetic approach using the Mx1-Cre system to specifically knockout (KO) Zeb1 in adult hematopoietic stem cells (HSCs) and their downstream progeny. Acute genetic deletion of Zeb1 led to rapid onset thymic atrophy and apoptosis driven loss of thymocytes and T cells. A profound cell-autonomous self-renewal defect and multi-lineage differentiation block was observed in Zeb1 KO HSCs. Loss of Zeb1 in HSCs activated transcriptional programs of deregulated HSC maintenance and multi-lineage differentiation genes, and of cell polarity, consisting of cytoskeleton, lipid metabolism/lipid membrane and cell adhesion related genes. Notably, Epithelial cell adhesion molecule (EpCAM) expression was prodigiously upregulated in Zeb1 KO HSCs, which correlated with their enhanced cell survival capacity and diminished differentiation in transplantation. Thus, Zeb1 acts as a crucial transcriptional regulator in hematopoiesis, co-ordinating HSC self-renewal and multi-lineage differentiation fates, in part, via EpCAM repression.
2020-07-02 | GSE153663 | GEO
Project description:Next Generation Sequencing of Wild Type and Zeb1-/- HSCs
| PRJNA643571 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-07-02 | GSE153664 | GEO
Project description:Zeb1, a zinc finger E-box binding homeobox epithelial-mesenchymal (EMT) transcription factor, confers properties of ‘stemness’, such as self-renewal, in cancer. Yet little is known about the function of Zeb1 in adult stem cells. Here, we used the hematopoietic system, as a well-established paradigm of stem cell biology, to evaluate Zeb1 mediated regulation of adult stem cells. We employed a conditional genetic approach using the Mx1-Cre system to specifically knockout (KO) Zeb1 in adult hematopoietic stem cells (HSCs) and their downstream progeny. Acute genetic deletion of Zeb1 led to rapid onset thymic atrophy and apoptosis driven loss of thymocytes and T cells. A profound cell-autonomous self-renewal defect and multi-lineage differentiation block was observed in Zeb1 KO HSCs. Loss of Zeb1 in HSCs activated transcriptional programs of deregulated HSC maintenance and multi-lineage differentiation genes, and of cell polarity, consisting of cytoskeleton, lipid metabolism/lipid membrane and cell adhesion related genes. Notably, Epithelial cell adhesion molecule (EpCAM) expression was prodigiously upregulated in Zeb1 KO HSCs, which correlated with their enhanced cell survival capacity and diminished differentiation in transplantation. Thus, Zeb1 acts as a crucial transcriptional regulator in hematopoiesis, co-ordinating HSC self-renewal and multi-lineage differentiation fates, in part, via EpCAM repression.
2020-10-01 | GSE154615 | GEO
Project description:Next Generation Sequencing of Wild Type and Gata2+/- HSCs
| PRJNA550447 | ENA
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. To determine the molecular mechanism of severe cytopenia in NHD13+ Tg mice, we purified Lin-Sca-1+c-Kit+CD34-Flt3-CD150+ HSCs from WT and NHD13+Tg mice at 4 month of age and perform the RNA-seq analysis. Methods: Trizol was used to extract RNA from FACS sorted CD150+CD34–Flt3–LSK viable cells. Total RNA was used for quality controls and for normalization of starting material. cDNA-libraries were generated with 10 ng of total RNA using the SMARTer Ultra Low RNA Kit for Illumina Sequencing according to the manufacturer’s indications. Sequencing was done using the Illumina Next-Gen Sequencing HiSeq platform with 30-45 million 75bp, paired-end reads. Results: We found 597 genes with significantly differential expression in NHD13+ HSCs, compared to WT controls (p<0.001). The expression of NUP98-HOXD13 up-regulated the expression of HOX genes, including Hoxa3, Hoxa5, Hoxa7, Hoxa9, Hoxb6, Hoxc5, Hoxc6, Hoxc8, Hoxc9 and Hoxd3, the important myeloid transcription factor Pbx3, cell cycle regulators, Cdk6 and Cdc25C, as well as the transcripts encoding the Ly6d surface membrane protein. We then performed pathway analyses, which showed that DNA duplication, DNA damage response and cell cycle-related genes, were more highly expressed in NHD13+ HSCs than WT HSCs, while multiple metabolic process-related gene pathways were downregulated. Conclusions: Our analyses demonstrate that the gene expression signature defined in murine NHD13+ MDS HSCs displays robust similarities with the gene expression profiles of human MDS cells, strongly suggesting that this murine MDS model can be used to accurately model human MDS.
2018-04-17 | GSE97911 | GEO
Project description:Gata2, a zinc finger TF, is essential for the generation and survival of HSCs in the embryo and has been implicated in the pathogenesis of AML, yet the requirement for Gata2 in adult HSCs and LSCs remains unclear. Using a conditional mouse model where Gata2 was deleted specifically in hematopoietic cells, we show that knockout of Gata2 leads to a rapid and complete cell-autonomous loss of adult HSCs. We then performed RNA-seq in sorted HSCs (LSK CD48- CD150+) from control and Gata2+/fl;Vav-iCre+ 8-to-10-week old mice.
2019-06-25 | GSE133248 | GEO
Project description:The goal of this study is to analyze the transcripts regulated by ZEB1.
2017-08-10 | GSE102337 | GEO