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Developmental cues license emergency megakaryopoiesis in hematopoietic stem cells [bulk RNA-seq & ATAC-seq]

ABSTRACT: Developmental cues license emergency megakaryopoiesis in hematopoietic stem cells [bulk RNA-seq & ATAC-seq]

PROVIDER: PRJNA679257 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13080800_1.fastq.gz	Fastqsanger.gz
	SRR13080800_2.fastq.gz	Fastqsanger.gz
	SRR13080801_1.fastq.gz	Fastqsanger.gz
	SRR13080801_2.fastq.gz	Fastqsanger.gz
	SRR13080802_1.fastq.gz	Fastqsanger.gz

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Developmental cues license emergency megakaryopoiesis in hematopoietic stem cells

Project description:Developmental cues license emergency megakaryopoiesis in hematopoietic stem cells

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Developmental cues license emergency megakaryopoiesis in hematopoietic stem cells [scATAC-seq]

Project description:Developmental cues license emergency megakaryopoiesis in hematopoietic stem cells [scATAC-seq]

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Developmental cues license emergency megakaryopoiesis in hematopoietic stem cells [scATAC-seq]

Project description:The fetal to adult switch in mouse hematopoietic stem cell (HSC) behavior is characterized by entry into quiescence and alterations in lineage output. Here we identify the ability of HSCs to undergo emergency megakaryopoiesis following acute inflammatory insult as an outcome of this developmental switch. Single cell accessibility mapping of fetal and adult HSCs resolves a heterogeneous chromatin landscape consistent with a two-step megakaryocyte lineage priming process. Importantly, we demonstrate that the accumulation of megakaryocyte primed HSCs is under the control of the developmentally restricted Lin28b RNA binding protein. Persistent Lin28b protein expression in postnatal HSCs delays the formation of a primed HSC pool and limits emergency megakaryopoiesis. Taken together, we identify Lin28b as a negative regulator of a megakaryocyte primed HSC state that is enforced at the chromatin level during unperturbed organismal development. These findings highlight the ontogenically timed onset of inflammatory responsiveness, with important implications for the delicate balance between host protection and tissue damage during neonatal life.

2022-05-14 | GSE161724 | GEO

Developmental cues license emergency megakaryopoiesis in hematopoietic stem cells [bulk RNA-seq & ATAC-seq]

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Developmental cues license emergency megakaryopoiesis in hematopoietic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-05-14 | GSE161725 | GEO

ABCC4 impacts megakaryopoiesis and protects megakaryocytes against 6-mercaptopurine induced cytotoxicity [RNA-seq Mouse]

Project description:The role of ABCC4, an ATP-binding cassette transporter, in the process of platelet formation, megakaryopoiesis, is unknown. Here, we show that ABCC4 is highly expressed in megakaryocytes (MKs). Mining of public genomic data (ATAC-seq and genome wide chromatin interactions, Hi-C) revealed that key megakaryopoiesis transcription factors (TFs) interacted with ABCC4 regulatory elements and likely accounted for high ABCC4 expression in MKs. Importantly these genomic interactions for ABCC4 ranked higher than for genes with known roles in megakaryopoiesis suggesting a role for ABCC4 in megakaryopoiesis. We then demonstrate that ABCC4 is required for optimal platelet formation as in vitro differentiation of fetal liver derived MKs from Abcc4-/- mice exhibited impaired proplatelet formation and polyploidization, features required for optimal megakaryopoiesis. Likewise, a human megakaryoblastic cell line, MEG-01 showed that acute ABCC4 inhibition markedly suppressed key processes in megakaryopoiesis and that these effects were related to reduced cAMP export and enhanced dissociation of a negative regulator of megakaryopoiesis, protein kinase A (PKA) from ABCC4. PKA activity concomitantly increased after ABCC4 inhibition which was coupled with significantly reduced GATA-1 expression, a TF needed for optimal megakaryopoiesis. Further, ABCC4 protected MKs from 6-mercaptopurine (6-MP) as Abcc4-/- mice show a profound reduction in MKs after 6-MP treatment. In total, our studies show that ABCC4 not only protects the MKs but is also required for maximal platelet production from MKs, suggesting modulation of ABCC4 function might be a potential therapeutic strategy to regulate platelet production.

2024-01-05 | GSE234628 | GEO

ABCC4 impacts megakaryopoiesis and protects megakaryocytes against 6-mercaptopurine induced cytotoxicity [RNA-seq Human]

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Maternal IL-10 restricts fetal emergency myelopoiesis [scRNA-seq]

Project description:Maternal IL-10 restricts fetal emergency myelopoiesis [scRNA-seq]

| PRJNA1005683 | ENA

Maternal IL-10 restricts fetal emergency myelopoiesis [scATAC-seq]

Project description:Maternal IL-10 restricts fetal emergency myelopoiesis [scATAC-seq]

| PRJNA1005686 | ENA

Maternal IL-10 restricts fetal emergency myelopoiesis [Bulk RNA-seq]

Project description:Maternal IL-10 restricts fetal emergency myelopoiesis [Bulk RNA-seq]

| PRJNA1005684 | ENA