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A Critical Role of RUNX1 in Governing Megakaryocyte-Primed Hematopoietic Stem Cell Differentiation

ABSTRACT: A Critical Role of RUNX1 in Governing Megakaryocyte-Primed Hematopoietic Stem Cell Differentiation

PROVIDER: PRJNA873137 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21203100_1.fastq.gz	Fastqsanger.gz
	SRR21203100_2.fastq.gz	Fastqsanger.gz
	SRR21203200_1.fastq.gz	Fastqsanger.gz
	SRR21203200_2.fastq.gz	Fastqsanger.gz
	SRR21203101_1.fastq.gz	Fastqsanger.gz

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A Critical Role of RUNX1 in Governing Megakaryocyte-Primed Hematopoietic Stem Cell Differentiation [RNA-seq]

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Project description:RUNX1 is crucial for multiple stages of hematopoiesis and its mutation can cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). We aim to study the role of RUNX1 in megakaryocyte-biased HSCs differentiation to megakaryocytes. Here, by using Runx1F/FMx1-Cre mouse model, we sorted CD41pos HSCs and CD41neg HSCs in both RUNX1 WT and KO, and compared their gene expression profiles.

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Project description:RUNX1 is crucial for multiple stages of hematopoiesis and its mutation can cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). We aim to study the role of RUNX1 in megakaryocyte-biased HSCs differentiation to megakaryocytes. Here, by using Runx1F/FMx1-Cre mouse model ,we sorted CD41pos HSCs and CD41neg HSCs in both RUNX1 WT and KO, and tested the RUNX1 direct binding targets in these cells genome.

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A critical role of RUNX1 in governing megakaryocyte-primed hematopoietic stem cell differentiation.

Project description:As a transcription factor in the RUNT domain core-binding factor family, RUNX1 is crucial in multiple stages of hematopoiesis, and its mutation can cause familial platelet disorder with a predisposition to acute myeloid leukemia. Previous work has established that RUNX1 is involved in the maturation of megakaryocytes (MKs) and the production of platelets. Recent studies have shown that there exists a subpopulation of hematopoietic stem cells (HSCs) with relatively high expression of von Willebrand factor and CD41 at the apex of the HSC hierarchy, termed MK-HSCs, which can give rise to MKs without going through the traditional differentiation trajectory from HSC via MPP (multipotent progenitors) and MEP (megakaryocyte-erythroid progenitor). Here, by using Runx1F/FMx1-Cre mouse model, we discovered that the MK-HSC to MK direct differentiation can occur within 1 cell division, and RUNX1 is an important regulator in the process. Runx1 knockout results in a drastic decrease in platelet counts and a severe defect in the differentiation from MK-HSCs to MKs. Single cell RNA sequencing (RNAseq) analysis shows that MK-HSCs have a distinct gene expression signature compared with non-MK-HSCs, and Runx1 deletion alters the platelet and MK-related gene expression in MK-HSCs. Furthermore, bulk RNAseq and Cut&Run analyses show that RUNX1 binds to multiple essential MK or platelet developmental genes, such as Spi1, Selp, and Itga2b and regulates their expressions in MK-HSCs. Thus, by modulating the expression of MK-related genes, RUNX1 governs the direct differentiation from MK-HSCs to MKs and platelets.

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A Critical Role of RUNX1 in Governing Megakaryocyte-Primed Hematopoietic Stem Cell Differentiation

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