{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Weinreb JT"],"funding":["American Australian Association","Vera and Joseph Dresner Foundation","American Cancer Society","NIDDK NIH HHS","Sidney Kimmel Foundation","Edward P Evans Foundation","NHLBI NIH HHS","NCI NIH HHS","US Department of Defense","National Institutes of Health","NIGMS NIH HHS"],"pagination":["627-640.e5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8258699"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["56(5)"],"pubmed_abstract":["Hematopoietic stem and progenitor cells (HSPCs) arise during embryonic development and are essential for sustaining the blood and immune systems throughout life. Tight regulation of HSPC numbers is critical for hematopoietic homeostasis. Here, we identified DEAD-box helicase 41 (Ddx41) as a gatekeeper of HSPC production. Using zebrafish ddx41 mutants, we unveiled a critical role for this helicase in regulating HSPC production at the endothelial-to-hematopoietic transition. We determined that Ddx41 suppresses the accumulation of R-loops, nucleic acid structures consisting of RNA:DNA hybrids and ssDNAs whose equilibrium is essential for cellular fitness. Excess R-loop levels in ddx41 mutants triggered the cGAS-STING inflammatory pathway leading to increased numbers of hemogenic endothelium a"],"journal":["Developmental cell"],"pubmed_title":["Excessive R-loops trigger an inflammatory cascade leading to increased HSPC production."],"pmcid":["PMC8258699"],"funding_grant_id":["T32 GM007491","P30 CA013330","R56 DK121738","T32 GM007288","R01 HL139487","F30 HL142161","R01 HL132071","R01 HL150832"],"pubmed_authors":["Tricomi B","Verma A","Ghazale N","Gupta V","Padgett RA","Bowman TV","Daniels NJ","Pradhan K","De Oliveira S","Weinreb JT","Potts KS"],"additional_accession":[]},"is_claimable":false,"name":"Excessive R-loops trigger an inflammatory cascade leading to increased HSPC production.","description":"Hematopoietic stem and progenitor cells (HSPCs) arise during embryonic development and are essential for sustaining the blood and immune systems throughout life. Tight regulation of HSPC numbers is critical for hematopoietic homeostasis. Here, we identified DEAD-box helicase 41 (Ddx41) as a gatekeeper of HSPC production. Using zebrafish ddx41 mutants, we unveiled a critical role for this helicase in regulating HSPC production at the endothelial-to-hematopoietic transition. We determined that Ddx41 suppresses the accumulation of R-loops, nucleic acid structures consisting of RNA:DNA hybrids and ssDNAs whose equilibrium is essential for cellular fitness. Excess R-loop levels in ddx41 mutants triggered the cGAS-STING inflammatory pathway leading to increased numbers of hemogenic endothelium a","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2026-05-30T15:09:51.83Z","creation":"2025-02-18T23:32:32.462Z"},"accession":"S-EPMC8258699","cross_references":{"pubmed":["33651979"],"doi":["10.1016/j.devcel.2021.02.006"]}}