Transcriptional plasticity, priming and commitment in hematopoietic lineages [CRISP-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA451342 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7053790.fastq.gz | Fastqsanger.gz | |||
| SRR7053800.fastq.gz | Fastqsanger.gz | |||
| SRR7053810.fastq.gz | Fastqsanger.gz | |||
| SRR7053820.fastq.gz | Fastqsanger.gz | |||
| SRR7053830.fastq.gz | Fastqsanger.gz |
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Project description:Transcriptional plasticity, priming and commitment in hematopoietic lineages
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Project description:Differentiation of adult hematopoietic stem cells (HSC) constantly produces the cell types of the blood and immune system. The dynamics of this process and the hierarchy of downstream oligopotent stem cell differentiation remain controversial. Here we dissect hematopoietic progenitor populations in a minimally biased fashion using extensive single cell sampling from murine bone marrow. We characterize the HSC population, define its quiescent transcriptional program and validate it with label retaining assays and cytokine mediated stimulations. Analysis of initial HSC commitment defines marked bifurcation of erythroid/megakaryocytic cells from myeloid/lymphoid lineages. Unexpectedly, we find states that mix transcription of pre-myeloid and pre-lymphoid genes. This suggests a model in which more than one differentiation trajectory can link HSC to several cell types. Dendritic cells are thus linked with both monocyte and lymphocyte precursors. Our data support a model of hematopoiesis balancing relaxation of an HSC quiescent state, gradual bifurcations and trans-differentiation.
2018-06-19 | GSE92575 | GEO
Project description:Differentiation of adult hematopoietic stem cells (HSC) constantly produces the cell types of the blood and immune system. The dynamics of this process and the hierarchy of downstream oligopotent stem cell differentiation remain controversial. Here we dissect hematopoietic progenitor populations in a minimally biased fashion using extensive single cell sampling from murine bone marrow. We characterize the HSC population, define its quiescent transcriptional program and validate it with label retaining assays and cytokine mediated stimulations. Analysis of initial HSC commitment defines marked bifurcation of erythroid/megakaryocytic cells from myeloid/lymphoid lineages. Unexpectedly, we find states that mix transcription of pre-myeloid and pre-lymphoid genes. This suggests a model in which more than one differentiation trajectory can link HSC to several cell types. Dendritic cells are thus linked with both monocyte and lymphocyte precursors. Our data support a model of hematopoiesis balancing relaxation of an HSC quiescent state, gradual bifurcations and trans-differentiation.
2018-06-19 | GSE113494 | GEO
Project description:Recent studies have documented genome-wide binding patterns of transcriptional regulators and their associated epigenetic marks in hematopoietic cell lineages. In order to determine how epigenetic marks are established and maintained during developmental progression, we have generated long-term cultures of hematopoietic progenitors by enforcing the expression of the E-protein antagonist Id2. Hematopoietic progenitors that express Id2 are multipotent and readily differentiate upon withdrawal of Id2 expression into committed B lineage cells, thus indicating a causative role for E2A (Tcf3) in promoting the B cell fate. Genome-wide analyses revealed that a substantial fraction of lymphoid and myeloid enhancers are premarked by the poised or active enhancer mark H3K4me1 in multipotent progenitors. Thus, in hematopoietic progenitors, multilineage priming of enhancer elements precedes commitment to the lymphoid or myeloid cell lineages. This SuperSeries is composed of the SubSeries listed below.
2011-09-01 | GSE30859 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-06-19 | GSE113495 | GEO
Project description:Transcriptional plasticity, priming and commitment in hematopoietic lineages [RNA-seq]
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Project description:Neural progenitor cells exhibit developmental plasticity, as they are able to commit to different developmental trajectories in response to external stimuli. How these decisions are stabilized at the molecular level remains a highly active area of research. One way to stably integrate external stimuli into cell fate decisions is through epigenetic marks. H4K16ac represents a unique epigenetic mark, as it modulates chromatin compaction and is the only known active histone modification that is transmitted intergenerationally. The deposition of H4K16ac is mediated by the evolutionarily conserved MSL acetyltransferase complex (MSLc), via its catalytic subunit MOF, and mutations in its components have been linked to neurodevelopmental disorders. To dissect the role of the MSLc, we employed a multi-pronged strategy combining both chronic and acute depletion models. Deletion of the MSLc structural backbone Msl1 in vivo resulted in embryonic lethality by E10, and single-cell multi-omics analysis revealed a systemic disruption in lineage commitment within the neuroectoderm. To distinguish primary molecular functions from secondary developmental consequences, we complemented this with a rapid degradation system in vitro, coupled to directed differentiation into two distinct neural lineages. We found that the MSLc facilitates accessibility at regulatory elements in the early stages of lineage commitment during neurogenesis. We observe a significant decrease in enhancer-promoter contacts in a specific subset of neurodevelopmental genes. In the absence of MSLc this gene group fails to reach adequate gene expression levels upon differentiation, resulting in abnormal morphology. Intriguingly, MSLc loss later on during differentiation does not phenocopy this. Our work reveals MSLc-mediated gene priming as a crucial mechanism potentiating the transcriptional activation of neurodevelopmental gene programs. Our study describes a new mode of epigenetic regulation which cements initial cell fate decisions and provides molecular insights into MSLc-associated developmental disorders.
2025-11-28 | GSE298008 | GEO
Project description:Neural progenitor cells exhibit developmental plasticity, as they are able to commit to different developmental trajectories in response to external stimuli. How these decisions are stabilized at the molecular level remains a highly active area of research. One way to stably integrate external stimuli into cell fate decisions is through epigenetic marks. H4K16ac represents a unique epigenetic mark, as it modulates chromatin compaction and is the only known active histone modification that is transmitted intergenerationally. The deposition of H4K16ac is mediated by the evolutionarily conserved MSL acetyltransferase complex (MSLc), via its catalytic subunit MOF, and mutations in its components have been linked to neurodevelopmental disorders. To dissect the role of the MSLc, we employed a multi-pronged strategy combining both chronic and acute depletion models. Deletion of the MSLc structural backbone Msl1 in vivo resulted in embryonic lethality by E10, and single-cell multi-omics analysis revealed a systemic disruption in lineage commitment within the neuroectoderm. To distinguish primary molecular functions from secondary developmental consequences, we complemented this with a rapid degradation system in vitro, coupled to directed differentiation into two distinct neural lineages. We found that the MSLc facilitates accessibility at regulatory elements in the early stages of lineage commitment during neurogenesis. We observe a significant decrease in enhancer-promoter contacts in a specific subset of neurodevelopmental genes. In the absence of MSLc this gene group fails to reach adequate gene expression levels upon differentiation, resulting in abnormal morphology. Intriguingly, MSLc loss later on during differentiation does not phenocopy this. Our work reveals MSLc-mediated gene priming as a crucial mechanism potentiating the transcriptional activation of neurodevelopmental gene programs. Our study describes a new mode of epigenetic regulation which cements initial cell fate decisions and provides molecular insights into MSLc-associated developmental disorders.
2025-11-28 | GSE298005 | GEO
Project description:Neural progenitor cells exhibit developmental plasticity, as they are able to commit to different developmental trajectories in response to external stimuli. How these decisions are stabilized at the molecular level remains a highly active area of research. One way to stably integrate external stimuli into cell fate decisions is through epigenetic marks. H4K16ac represents a unique epigenetic mark, as it modulates chromatin compaction and is the only known active histone modification that is transmitted intergenerationally. The deposition of H4K16ac is mediated by the evolutionarily conserved MSL acetyltransferase complex (MSLc), via its catalytic subunit MOF, and mutations in its components have been linked to neurodevelopmental disorders. To dissect the role of the MSLc, we employed a multi-pronged strategy combining both chronic and acute depletion models. Deletion of the MSLc structural backbone Msl1 in vivo resulted in embryonic lethality by E10, and single-cell multi-omics analysis revealed a systemic disruption in lineage commitment within the neuroectoderm. To distinguish primary molecular functions from secondary developmental consequences, we complemented this with a rapid degradation system in vitro, coupled to directed differentiation into two distinct neural lineages. We found that the MSLc facilitates accessibility at regulatory elements in the early stages of lineage commitment during neurogenesis. We observe a significant decrease in enhancer-promoter contacts in a specific subset of neurodevelopmental genes. In the absence of MSLc this gene group fails to reach adequate gene expression levels upon differentiation, resulting in abnormal morphology. Intriguingly, MSLc loss later on during differentiation does not phenocopy this. Our work reveals MSLc-mediated gene priming as a crucial mechanism potentiating the transcriptional activation of neurodevelopmental gene programs. Our study describes a new mode of epigenetic regulation which cements initial cell fate decisions and provides molecular insights into MSLc-associated developmental disorders.
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Project description:Combinatorial actions of relatively few transcription factors control hematopoietic differentiation. To investigate this process in erythro-megakaryopoiesis, we correlated the genome-wide chromatin occupancy signatures of four master hematopoietic transcription factors (GATA1, GATA2, SCL/TAL1 and FLI1) and three diagnostic histone modification marks with the gene expression changes that occur during development of primary megakaryocytes (MEG) and erythroblasts (ERY) from murine fetal liver hematopoietic stem/progenitor cells. We identified a robust, genome-wide mechanism of MEG-specific lineage priming by a previously described stem/progenitor cell-expressed transcription factor heptad (GATA2, LYL1, SCL/TAL1, FLI1, ERG, RUNX1, LMO2) binding to MEG-specific cis-regulatory modules in multipotential hematopoietic progenitors. This is followed by genome-wide GATA factor switching that mediates further induction of MEG-specific genes following lineage commitment. Interaction between GATA and ETS factors appears to be a key determinant of these processes. In contrast, ERY-specific lineage priming occurs is biased toward GATA2-independent mechanisms. In addition to its role in MEG lineage priming, GATA2 plays an extensive role in late megakaryopoiesis as a transcriptional repressor at loci defined by a specific DNA signature. Our findings reveal important new insights into how ERY and MEG lineages arise from a common bipotential precursor via overlapping and divergent functions of shared hematopoietic transcription factors. Gene expression changes during the development of primary megakaryocytes (MEG) and erythroblasts (ERY) from murine fetal liver hematopoietic stem/progenitor cells
2013-08-09 | E-GEOD-49664 | biostudies-arrayexpress