{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T16:39:06Z","timestamp":1789922346919,"version":"4.0.1"},"reference-count":72,"publisher":"National Academy of Sciences","issue":"49","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["(32030032"],"award-info":[{"award-number":["(32030032"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,12,9]]},"abstract":"<jats:p>\n                    During vertebrate embryogenesis, hematopoietic stem and progenitor cells (HSPCs) originate from hemogenic endothelium (HE) in the dorsal aorta through endothelial-to-hematopoietic transition (EHT). While basal inflammation is essential for this process, excessive immune activation disrupts HSPC emergence. Here, we identify angiotensin-converting enzyme 2 (Ace2), a key component of renin\u2013angiotensin system, as a crucial anti-inflammatory regulator of embryonic hematopoiesis in zebrafish and mice. Loss of Ace2 impairs HE specification and reduces nascent HSPC production. Mechanistically, transcriptomic profiling reveals that\n                    <jats:italic toggle=\"yes\">ace2<\/jats:italic>\n                    deficiency leads to aberrant activation of NLR family pyrin domain containing 3 (Nlrp3) signaling and pyroptosis in vascular endothelial cells. Importantly, pharmacological inhibition of Nlrp3 or Caspase-1 restores HSPC emergence upon\n                    <jats:italic toggle=\"yes\">ace2<\/jats:italic>\n                    deficiency, consistent with treatment with exogenous angiotensin-(1\u20137) [Ang-(1\u20137)], a downstream product of Ace2 enzymatic activity. Moreover, Ace2 knockdown in mouse embryos phenocopies the defects in zebrafish, demonstrating evolutionary conservation of ACE2 in developmental hematopoiesis in mammals. Together, our findings uncover an essential role for ACE2 in maintaining a permissive inflammatory environment for HSPC development and suggest therapeutic potential for targeting the ACE2\/Ang-(1\u20137)\/Nlrp3-pyroptosis axis in inflammatory hematopoietic disorders.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2515641122","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T18:38:55Z","timestamp":1764959935000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Ace2 safeguards embryonic hematopoietic stem and progenitor cell production by restraining Nlrp3-mediated pyroptosis"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3996-2551","authenticated-orcid":false,"given":"Jun","family":"Xia","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University","place":["Qingdao, China"]},{"name":"State Key Laboratory of Organ Regeneration and Reconstruction Beijing Institute for Stem Cell and Regenerative Medicine, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxue","family":"Shen","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yining","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Regeneration and Reconstruction Beijing Institute for Stem Cell and Regenerative Medicine, Institute of Zoology, University of Chinese Academy of 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