biostudies-literatureShaligram SSNational Institute of Neurological Disorders and StrokeMichael Ryan Zodda FoundationAmerican Heart Association-American Stroke AssociationFondation LeducqNational Heart, Lung, and Blood InstituteNHLBI NIH HHSU.S. Department of DefenseNINDS NIH HHSBarrow Neurological FoundationAmerican Health Assistance Foundation494-504https://www.ebi.ac.uk/biostudies/studies/S-EPMC9021325biostudies-literatureUnknown13(3)We have previously demonstrated that deletion of activin receptor-like kinase 1 (Alk1) or endoglin in a fraction of endothelial cells (ECs) induces brain arteriovenous malformations (bAVMs) in adult mice upon angiogenic stimulation. Here, we addressed three related questions: (1) could Alk1^- mutant bone marrow (BM)-derived ECs (BMDECs) cause bAVMs? (2) is Alk1^- ECs clonally expended during bAVM development? and (3) is the number of mutant ECs correlates to bAVM severity? For the first question, we transplanted BM from PdgfbiCreER;Alk1^2f/2f mice (EC-specific tamoxifen-inducible Cre with Alk1-floxed alleles) into wild-type mice, and then induced bAVMs by intra-brain injection of an adeno-associated viral vector expressing vascular endothelial growth factor anTranslational stroke researchBone Marrow-Derived Alk1 Mutant Endothelial Cells and Clonally Expanded Somatic Alk1 Mutant Endothelial Cells Contribute to the Development of Brain Arteriovenous Malformations in Mice.PMC9021325ATTRACTHL12277420POST35120371PR161205NS027713NS112819R01 HL122774R01 NS112819R01 NS027713Shaligram SSdo Prado LMa LArnold TTang CLi QZhang ROh SPSu HSantander NLuo MPan FPan PZhu WWeiss MLiang RfalseBone Marrow-Derived Alk1 Mutant Endothelial Cells and Clonally Expanded Somatic Alk1 Mutant Endothelial Cells Contribute to the Development of Brain Arteriovenous Malformations in Mice.We have previously demonstrated that deletion of activin receptor-like kinase 1 (Alk1) or endoglin in a fraction of endothelial cells (ECs) induces brain arteriovenous malformations (bAVMs) in adult mice upon angiogenic stimulation. Here, we addressed three related questions: (1) could Alk1^- mutant bone marrow (BM)-derived ECs (BMDECs) cause bAVMs? (2) is Alk1^- ECs clonally expended during bAVM development? and (3) is the number of mutant ECs correlates to bAVM severity? For the first question, we transplanted BM from PdgfbiCreER;Alk1^2f/2f mice (EC-specific tamoxifen-inducible Cre with Alk1-floxed alleles) into wild-type mice, and then induced bAVMs by intra-brain injection of an adeno-associated viral vector expressing vascular endothelial growth factor an2022-01-01T00:00:00Z2022 Jun2025-04-26T23:03:07.168Z2025-04-06T17:24:33.159ZS-EPMC90213253467414410.1007/s12975-021-00955-9