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Mettl16 promotes hematopoietic stem and progenitor cell expansion in embryonic hematopoiesis

ABSTRACT: Mettl16 promotes hematopoietic stem and progenitor cell expansion in embryonic hematopoiesis

PROVIDER: PRJNA934075 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23410300_1.fastq.gz	Fastqsanger.gz
	SRR23410300_2.fastq.gz	Fastqsanger.gz
	SRR23410301_1.fastq.gz	Fastqsanger.gz
	SRR23410301_2.fastq.gz	Fastqsanger.gz
	SRR23433707_1.fastq.gz	Fastqsanger.gz

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Mettl16 promotes hematopoietic stem and progenitor cell expansion in embryonic hematopoiesis [m6A-Seq]

Project description:The RNA N6-methyladenosine (m6A) modification has emerged as an essential regulator of vertebrate embryogenesis and malignancies. However, its functions and underlying molecular mechanisms in the expansion of hematopoietic stem and progenitor cells (HSPCs) during early embryonic development remain elusive. Here we show that Mettl16, an RNA methyltransferase identified recently, is specifically required for HSPC expansion during zebrafish early embryonic development in an m6A-dependent manner. In mettl16 deficient embryos, HSPCs exhibit defective proliferation capacity due to G0/G1 arrest. Mechanistically, HSPC proliferation is blocked by impaired methyltransferase function of Mettl16 in vivo. We identify cell cycle gene mybl2b as a novel direct m6A target of Mettl16, and Mettl16 deficiency destabilizes mybl2b mRNA, which is mediated by m6A reader Igf2bp1. Moreover, we revealed that the METTL16-m6A-MYBL2-IGF2BP1 signaling axis in G1/S progression is conserved in humans. Collectively, our findings demonstrate the critical function of m6A modification deposited by Mettl16 in HSPC expansion during early embryonic development.

2024-03-04 | GSE225136 | GEO

Mettl16 promotes hematopoietic stem and progenitor cell expansion in embryonic hematopoiesis [RNA-seq]

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Mettl16 promotes hematopoietic stem and progenitor cell expansion in embryonic hematopoiesis [m6A-Seq]

Project description:Mettl16 promotes hematopoietic stem and progenitor cell expansion in embryonic hematopoiesis [m6A-Seq]

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Mettl16 promotes hematopoietic stem and progenitor cell expansion in embryonic hematopoiesis [RNA-seq]

Project description:Mettl16 promotes hematopoietic stem and progenitor cell expansion in embryonic hematopoiesis [RNA-seq]

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Slc20a1b is essential for hematopoietic stem/progenitor cell expansion in zebrafish

Project description:Hematopoietic stem and progenitor cells (HSPCs) are able to self-renew and can give rise to all blood lineages throughout their lifetime, yet the mechanisms regulating HSPC development have yet to be discovered. In this study, we characterized a hematopoiesis defective zebrafish mutant line named smu07, which was obtained from our previous forward genetic screening, and found the HSPC expansion deficiency in the mutant. Positional cloning identified that slc20a1b, which encodes a sodium phosphate cotransporter, contributed to the smu07 blood phenotype. Further analysis demonstrated that mutation of slc20a1b affects HSPC expansion through cell cycle arrest at G2/M phases in a cell-autonomous manner. Our study shows that slc20a1b is a vital regulator for HSPC proliferation in zebrafish early hematopoiesis and provides valuable insights into HSPC development.

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A bone marrow stromal secretome screen identifies semaphorin 3A as a regulator of stress hematopoiesis

Project description:Bone marrow mesenchymal stromal cells (MSCs) are a major source of secreted factors that control hematopoietic stem and progenitor cell (HSPC) function. We previously reported the generation of revitalized MSCs (rMSCs), which support functional HSCs in culture more effectively than control MSCs. In a secretomic screen using rMSCs, we identified semaphorin 3A (SEM3A) as a secreted factor upregulated as part of a pro-inflammatory signature that may underly HSPC expansion by rMSCs. Similarly, SEM3A expression is upregulated by BM-MSCs in vivo in response to hematopoietic stress. Recombinant SEM3A directly promotes HSPC quiescence ex vivo. Analysis of a SEM3A loss of function mutation in vivo revealed hematopoietic progenitor expansion and accelerated recovery after myeloablation, consistent with a role for SEM3A in regulating the HSPC stress response. This work highlights proteomic screening using rMSCs as a method to identify novel secreted niche factors and uncovers a novel role for SEM3A in promoting HSPC quiescence in stress hematopoiesis.

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Ageing-associated proteome and acetylome of hematopoietic progenitor cells

Project description:Ageing-associated proteome and acetylome of hematopoietic progenitor cells

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The splicing factor Prpf31 is required for hematopoietic stem and progenitor cell expansion during zebrafish embryogenesis

Project description:Pre-mRNA splicing is a precise regulated process, and is crucial for system development and homeostasis maintenance. Mutations in spliceosomal components have been found in various hematopoietic malignancies (HMs), and have been considered as oncogenic derivers of HMs. However, the role of spliceosomal components in normal and malignant hematopoiesis remain largely unknown. Pre-mRNA processing factor 31 (PRPF31) is a constitutive spliceosomal component, which mutations are associated with autosomal dominant retinitis pigmentosa. PRPF31 was found to be mutated in several HMs, but the function of PRPF31 in normal hematopoiesis has not been explored. In this study, we generated a prpf31 knockout zebrafish line, and discovered that prpf31 mutants exhibited severe defects in hematopoietic stem and progenitor cell (HSPC) expansion and its sequentially differentiated lineages. Immunofluorescence results showed that Prpf31 deficient HSPCs underwent malformed mitosis and M phase arrest during HSPC expansion. Transcriptome analysis and experimental validations revealed that Prpf31 deficiency extensively perturbed the alternative splicing of mitosis-related genes. Collectively, our findings elucidate a previously undescribed role for Prpf31 in HSPC expansion, through regulating the alternative splicing of mitosis-related genes.

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Hematopoietic Stem/Progenitor Cell Expansion Without Differentiation is Achieved in Zwitterionic Hydrogels

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Mettl16 promotes hematopoietic stem and progenitor cell expansion in embryonic hematopoiesis

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

2024-03-03 | GSE225137 | GEO