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Proteasome Function is Required for Platelet Production

ABSTRACT: Proteasome Function is Required for Platelet Production

PROVIDER: PRJNA251563 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2144270.fastq.gz	Fastqsanger.gz
	SRR2144271.fastq.gz	Fastqsanger.gz
	SRR2144269.fastq.gz	Fastqsanger.gz
	SRR2144269_1.fastq.gz	Fastqsanger.gz
	SRR2144269_2.fastq.gz	Fastqsanger.gz

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Proteasome Function is Required for Platelet Production

Project description:RNA-seq expression analysis of transcripts encoding proteasome subunits in human CD34+ cord blood cell-derived megakaryocytes and mouse bone marrow-derived megakaryocytes. Analysis of transcript expression in human CD34+ cord blood cell-derived megakaryocytes and mouse bone marrow-derived megakaryocytes.

2015-01-31 | E-GEOD-58202 | biostudies-arrayexpress

Proteasome Function is Required for Platelet Production

Project description:RNA-seq expression analysis of transcripts encoding proteasome subunits in human CD34+ cord blood cell-derived megakaryocytes and mouse bone marrow-derived megakaryocytes.

2015-01-31 | GSE58202 | GEO

Proteasome function is required for platelet production.

Project description:The proteasome inhibiter bortezomib has been successfully used to treat patients with relapsed multiple myeloma; however, many of these patients become thrombocytopenic, and it is not clear how the proteasome influences platelet production. Here we determined that pharmacologic inhibition of proteasome activity blocks proplatelet formation in human and mouse megakaryocytes. We also found that megakaryocytes isolated from mice deficient for PSMC1, an essential subunit of the 26S proteasome, fail to produce proplatelets. Consistent with decreased proplatelet formation, mice lacking PSMC1 in platelets (Psmc1(fl/fl) Pf4-Cre mice) exhibited severe thrombocytopenia and died shortly after birth. The failure to produce proplatelets in proteasome-inhibited megakaryocytes was due to upregulation and hyperactivation of the small GTPase, RhoA, rather than NF-κB, as has been previously suggested. Inhibition of RhoA or its downstream target, Rho-associated protein kinase (ROCK), restored megakaryocyte proplatelet formation in the setting of proteasome inhibition in vitro. Similarly, fasudil, a ROCK inhibitor used clinically to treat cerebral vasospasm, restored platelet counts in adult mice that were made thrombocytopenic by tamoxifen-induced suppression of proteasome activity in megakaryocytes and platelets (Psmc1(fl/fl) Pdgf-Cre-ER mice). These results indicate that proteasome function is critical for thrombopoiesis, and suggest inhibition of RhoA signaling as a potential strategy to treat thrombocytopenia in bortezomib-treated multiple myeloma patients.

| S-EPMC4151230 | biostudies-literature

Mitochondrial gene expression is required for platelet function and blood clotting

Project description:Mitochondrial gene expression is required for platelet function and blood clotting

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Shared roles for Scl and Lyl1 in murine platelet production and function

Project description:The Stem Cell Leukemia (Scl or Tal1) protein forms part of a multimeric transcription factor complex required for normal megakaryopoiesis. However, unlike other members of this complex such as Gata1, Fli1 and Runx1, mutations of Scl have not been observed as a cause of inherited thrombocytopenia. We postulated that functional redundancy with its closely related family member, Lymphoblastic Leukemia 1 (Lyl1) might explain this observation. To determine if Lyl1 can substitute for Scl in megakaryopoiesis, we examined the platelet phenotype of mice lacking one or both factors in megakaryocytes. Conditional Scl knockout mice crossed with transgenic mice expressing Cre recombinase under the control of the mouse platelet factor 4 (Pf4) promoter generated megakaryocytes with markedly reduced but not absent Scl. These Pf4SclcKO mice had mild thrombocytopenia and subtle defects in platelet aggregation. However, Pf4SclcKO mice generated on a Lyl1-null background (double knockout, DKO mice) had severe macrothrombocytopenia, abnormal megakaryocyte morphology, defective pro-platelet formation and markedly impaired platelet aggregation. DKO megakaryocytes, but not single knockouts, had reduced expression of Gata1, Fli1, Nfe2 and many other genes that cause inherited thrombocytopenia. These gene expression changes were significantly associated with shared Scl and Lyl1 E-box binding sites that were also enriched for Gata1, Ets and Runx1 motifs. Thus, Scl and Lyl1 share functional roles in platelet production and function by regulating expression of partner proteins including Gata1 and Fli1. We propose that this functional redundancy provides one explanation for the absence of Scl and Lyl1 mutations as a cause of inherited thrombocytopenia.

2020-12-21 | GSE125025 | GEO

Shared roles for Scl and Lyl1 in murine platelet production and function

Project description:Shared roles for Scl and Lyl1 in murine platelet production and function

| PRJNA514993 | ENA

MLL3/4 Direct a Gene-expression Program Required for Efficient Platelet Production [RNA-seq]

Project description:MLL3/4 Direct a Gene-expression Program Required for Efficient Platelet Production [RNA-seq]

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MLL3/4 Direct a Gene-expression Program Required for Efficient Platelet Production [CUT&RUN]

Project description:MLL3/4 Direct a Gene-expression Program Required for Efficient Platelet Production [CUT&RUN]

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MLL3/4 Direct a Gene-expression Program Required for Efficient Platelet Production [RNA-seq]

Project description:MLL3 and MLL4 are the mjor histone lysine methyltransferases for the active enhance mark H3K4me1. We observed that platelet counts are dramatically decreased in the MLL3/4 SET-deletion mice. Cultured megakaryocytes from MLL3/4 SET-deletion fetal liver were used for RNA-seq analysis to investigate the changes in gene expression. We also performed CUT&RUN analysis to examine the changes in enhncers that may regulate those gene expression. We included PTIP in this study, because it is an important co-factor of the MLL3/4 complex, and knockout of PTIP also leads to decreased platelet production.

2025-05-13 | GSE255020 | GEO