{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T20:56:16Z","timestamp":1782248176222,"version":"3.54.5"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2013,10,10]],"date-time":"2013-10-10T00:00:00Z","timestamp":1381363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P01-CA70970"],"award-info":[{"award-number":["P01-CA70970"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01-HL073781"],"award-info":[{"award-number":["R01-HL073781"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["T32-HL007525"],"award-info":[{"award-number":["T32-HL007525"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>PIG-A is an X-linked gene required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors; thus, PIG-A mutant cells have a deficiency or absence of all GPI-anchored proteins (GPI-APs). Acquired mutations in hematopoietic stem cells result in the disease paroxysmal nocturnal hemoglobinuria, and hypomorphic germline PIG-A mutations lead to severe developmental abnormalities, seizures, and early death. Human induced pluripotent stem cells (iPSCs) can differentiate into cell types derived from all three germ layers, providing a novel developmental system for modeling human diseases. Using PIG-A gene targeting and an inducible PIG-A expression system, we have established, for the first time, a conditional PIG-A knockout model in human iPSCs that allows for the production of GPI-AP-deficient blood cells. PIG-A-null iPSCs were unable to generate hematopoietic cells or any cells expressing the CD34 marker and were defective in generating mesodermal cells expressing KDR\/VEGFR2 (kinase insert domain receptor) and CD56 markers. In addition, PIG-A-null iPSCs had a block in embryonic development prior to mesoderm differentiation that appears to be due to defective signaling through bone morphogenetic protein 4. However, early inducible PIG-A transgene expression allowed for the generation of GPI-AP-deficient blood cells. This conditional PIG-A knockout model should be a valuable tool for studying the importance of GPI-APs in hematopoiesis and human development.<\/jats:p>","DOI":"10.5966\/sctm.2013-0069","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T13:36:45Z","timestamp":1381498605000},"page":"819-829","source":"Crossref","is-referenced-by-count":18,"title":["Generation of Glycosylphosphatidylinositol Anchor Protein-Deficient Blood Cells From Human Induced Pluripotent Stem Cells"],"prefix":"10.1093","volume":"2","author":[{"given":"Xuan","family":"Yuan","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan M.","family":"Braunstein","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Ye","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Stem Cell Program, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyndi F.","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Stem Cell Program, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guibin","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, 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