Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression II
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ABSTRACT:
PROVIDER: PRJNA810085 | ENA |
REPOSITORIES: ENA
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Project description:Hematopoietic stem and progenitor cells (HSPCs) originate from an endothelial-to-hematopoietic transition (EHT) during embryogenesis. Characterization of early hemogenic endothelial (HE) cells is required to understand what drives hemogenic specification and to accurately define cells capable of undergoing EHT. Using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq), we defined the early subpopulation of pre-HE cells based on both surface markers and transcriptomes. We identified the transcription factor Meis1 as an essential regulator of hemogenic cell specification in the embryo prior to Runx1 expression. Meis1 is expressed at the earliest stages of EHT and distinguishes pre-HE cells primed towards the hemogenic trajectory from the arterial endothelial cells that continue towards a vascular fate. Endothelial-specific deletion of Meis1 impaired the formation of functional Runx1-expressing HE which significantly impeded the emergence of pre-HSPC via EHT. Our findings implicate Meis1 in a critical fate-determining step for establishing EHT potential in endothelial cells.
2023-02-02 | GSE196047 | GEO
Project description:Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression
| PRJNA803157 | ENA
Project description:Hematopoietic stem and progenitor cells (HSPCs) originate from an endothelial-to-hematopoietic transition (EHT) during embryogenesis. Characterization of early hemogenic endothelial (HE) cells is required to understand what drives hemogenic specification and to accurately define cells capable of undergoing EHT. Using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq), we defined the early subpopulation of pre-HE cells based on both surface markers and transcriptomes. We identified the transcription factor Meis1 as an essential regulator of hemogenic cell specification in the embryo prior to Runx1 expression. Meis1 is expressed at the earliest stages of EHT and distinguishes pre-HE cells primed towards the hemogenic trajectory from the arterial endothelial cells that continue towards a vascular fate. Endothelial-specific deletion of Meis1 impaired the formation of functional Runx1-expressing HE which significantly impeded the emergence of pre-HSPC via EHT. Our findings implicate Meis1 in a critical fate-determining step for establishing EHT potential in endothelial cells.
2023-02-22 | GSE197400 | GEO
Project description:Hematopoietic stem and progenitor cells (HSPCs) originate from an endothelial-to-hematopoietic transition (EHT) during embryogenesis. Characterization of early hemogenic endothelial (HE) cells is required to understand what drives hemogenic specification and to accurately define cells capable of undergoing EHT. Using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq), we defined the early subpopulation of pre-HE cells based on both surface markers and transcriptomes. We identified the transcription factor Meis1 as an essential regulator of hemogenic cell specification in the embryo prior to Runx1 expression. Meis1 is expressed at the earliest stages of EHT and distinguishes pre-HE cells primed towards the hemogenic trajectory from the arterial endothelial cells that continue towards a vascular fate. Endothelial-specific deletion of Meis1 impaired the formation of functional Runx1-expressing HE which significantly impeded the emergence of pre-HSPC via EHT. Our findings implicate Meis1 in a critical fate-determining step for establishing EHT potential in endothelial cells.
2023-02-22 | GSE197244 | GEO
Project description:Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression [CITE-seq]
| PRJNA809477 | ENA
Project description:Meis1 as an essential regulator of hemogenic cell specification in the embryo prior to Runx1 expression
| PRJEB52790 | ENA
Project description:During ontogeny the transcription factor RUNX1 governs the emergence of definitive hematopoietic cells from specialized endothelial cells, called hemogenic endothelium (HE). The ultimate consequence of this endothelial-to-hematopoietic transition is the concomitant activation of the hematopoietic program and down-regulation of the endothelial program. However, due to the rare and transient nature of the HE, little is known about the initial role of RUNX1 within this population. We therefore developed and implemented a highly sensitive DamID (DNA adenine methyltransferase identification) based methodology, including a novel data analysis pipeline, to map early RUNX1 transcriptional targets in HE cells. This novel transcription factor binding site identification protocol should be widely applicable to other low abundance cell types and factors. Integration of the RUNX1 binding profile with gene expression data revealed an unexpected early role for RUNX1 as a positive regulator of cell adhesion and migration associated genes within the HE. This suggests that RUNX1 orchestrates HE cell positioning and integration prior to the release of hematopoietic cells. Overall, our genome-wide analysis of the RUNX1 binding and transcriptional profile in the HE provides a novel comprehensive resource of target genes that will facilitate the precise dissection of the role of RUNX1 in early blood development. mRNA profiles of mouse ES derived Haemogenonic Endothelium (cKit+ Tie2+ CD41-) were generated by deep sequencing using the SOLiD 5500XL Genetic Analyser (Applied Biosystems). Two biological duplicates of each of the following lines was sequenced: iDam & BryGFP (both wt background) and iDam_runx1-/- (iDamko) & Ainv18_runx1-/- (Ainv18ko). The latter two lines are Runx1 knockouts.
2014-08-05 | E-GEOD-55310 | biostudies-arrayexpress
Project description:During ontogeny the transcription factor RUNX1 governs the emergence of definitive hematopoietic cells from specialized endothelial cells, called hemogenic endothelium (HE). The ultimate consequence of this endothelial-to-hematopoietic transition is the concomitant activation of the hematopoietic program and down-regulation of the endothelial program. However, due to the rare and transient nature of the HE, little is known about the initial role of RUNX1 within this population. We therefore developed and implemented a highly sensitive DamID (DNA adenine methyltransferase identification) based methodology, including a novel data analysis pipeline, to map early RUNX1 transcriptional targets in HE cells. This novel transcription factor binding site identification protocol should be widely applicable to other low abundance cell types and factors. Integration of the RUNX1 binding profile with gene expression data revealed an unexpected early role for RUNX1 as a positive regulator of cell adhesion and migration associated genes within the HE. This suggests that RUNX1 orchestrates HE cell positioning and integration prior to the release of hematopoietic cells. Overall, our genome-wide analysis of the RUNX1 binding and transcriptional profile in the HE provides a novel comprehensive resource of target genes that will facilitate the precise dissection of the role of RUNX1 in early blood development. Runx1b binding profiles of mouse ES derived haemogenonic endothelium were generated by deep sequencing using the SOLiD 3 or 4 System (Applied Biosystems). Three biological duplicates and three technical replicates where sequenced for each of the following lines: iDam_runx1-/- (iDamko) and iRunx1b::Dam_runx1-/- (iRunx1b::Damko)
2014-08-05 | E-GEOD-55308 | biostudies-arrayexpress
Project description:During ontogeny the transcription factor RUNX1 governs the emergence of definitive hematopoietic cells from specialized endothelial cells, called hemogenic endothelium (HE). The ultimate consequence of this endothelial-to-hematopoietic transition is the concomitant activation of the hematopoietic program and down-regulation of the endothelial program. However, due to the rare and transient nature of the HE, little is known about the initial role of RUNX1 within this population. We therefore developed and implemented a highly sensitive DamID (DNA adenine methyltransferase identification) based methodology, including a novel data analysis pipeline, to map early RUNX1 transcriptional targets in HE cells. This novel transcription factor binding site identification protocol should be widely applicable to other low abundance cell types and factors. Integration of the RUNX1 binding profile with gene expression data revealed an unexpected early role for RUNX1 as a positive regulator of cell adhesion and migration associated genes within the HE. This suggests that RUNX1 orchestrates HE cell positioning and integration prior to the release of hematopoietic cells. Overall, our genome-wide analysis of the RUNX1 binding and transcriptional profile in the HE provides a novel comprehensive resource of target genes that will facilitate the precise dissection of the role of RUNX1 in early blood development.
2014-08-05 | GSE55310 | GEO
Project description:During ontogeny the transcription factor RUNX1 governs the emergence of definitive hematopoietic cells from specialized endothelial cells, called hemogenic endothelium (HE). The ultimate consequence of this endothelial-to-hematopoietic transition is the concomitant activation of the hematopoietic program and down-regulation of the endothelial program. However, due to the rare and transient nature of the HE, little is known about the initial role of RUNX1 within this population. We therefore developed and implemented a highly sensitive DamID (DNA adenine methyltransferase identification) based methodology, including a novel data analysis pipeline, to map early RUNX1 transcriptional targets in HE cells. This novel transcription factor binding site identification protocol should be widely applicable to other low abundance cell types and factors. Integration of the RUNX1 binding profile with gene expression data revealed an unexpected early role for RUNX1 as a positive regulator of cell adhesion and migration associated genes within the HE. This suggests that RUNX1 orchestrates HE cell positioning and integration prior to the release of hematopoietic cells. Overall, our genome-wide analysis of the RUNX1 binding and transcriptional profile in the HE provides a novel comprehensive resource of target genes that will facilitate the precise dissection of the role of RUNX1 in early blood development.
2014-08-05 | GSE55308 | GEO