دورية أكاديمية
ACVR1 R206H extends inflammatory responses in human induced pluripotent stem cell-derived macrophages.
العنوان: | ACVR1 R206H extends inflammatory responses in human induced pluripotent stem cell-derived macrophages. |
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المؤلفون: | Matsuo K; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, USA; The Institute for Human Genetics, University of California, San Francisco, CA, USA; The Program in Craniofacial Biology, University of California, San Francisco, CA, USA., Lepinski A; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, USA; The Institute for Human Genetics, University of California, San Francisco, CA, USA; The Program in Craniofacial Biology, University of California, San Francisco, CA, USA; Division of Graduate Medical Sciences, Boston University School of Medicine, Boston, MA, USA., Chavez RD; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, USA; The Institute for Human Genetics, University of California, San Francisco, CA, USA; The Program in Craniofacial Biology, University of California, San Francisco, CA, USA., Barruet E; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, USA; The Institute for Human Genetics, University of California, San Francisco, CA, USA; The Program in Craniofacial Biology, University of California, San Francisco, CA, USA., Pereira A; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, USA; The Institute for Human Genetics, University of California, San Francisco, CA, USA; The Program in Craniofacial Biology, University of California, San Francisco, CA, USA., Moody TA; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, USA; The Institute for Human Genetics, University of California, San Francisco, CA, USA; The Program in Craniofacial Biology, University of California, San Francisco, CA, USA., Ton AN; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, USA; The Institute for Human Genetics, University of California, San Francisco, CA, USA; The Program in Craniofacial Biology, University of California, San Francisco, CA, USA., Sharma A; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, USA; The Institute for Human Genetics, University of California, San Francisco, CA, USA; The Program in Craniofacial Biology, University of California, San Francisco, CA, USA., Hellman J; Department of Anesthesia and Perioperative Care, University of California, San Francisco, USA., Tomoda K; Gladstone Institute of Cardiovascular Disease, San Francisco, CA, USA., Nakamura MC; Medical Service, San Francisco Veterans Affairs Healthcare System, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA., Hsiao EC; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA, USA; The Institute for Human Genetics, University of California, San Francisco, CA, USA; The Program in Craniofacial Biology, University of California, San Francisco, CA, USA. Electronic address: Edward.hsiao@ucsf.edu. |
المصدر: | Bone [Bone] 2021 Dec; Vol. 153, pp. 116129. Date of Electronic Publication: 2021 Jul 24. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 8504048 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2763 (Electronic) Linking ISSN: 18732763 NLM ISO Abbreviation: Bone Subsets: MEDLINE |
أسماء مطبوعة: | Publication: New York : Elsevier Science Original Publication: Elmsford, NY : Pergamon Press, c1985- |
مواضيع طبية MeSH: | Induced Pluripotent Stem Cells*/metabolism , Myositis Ossificans* , Ossification, Heterotopic*, Activin Receptors, Type I/genetics ; Activin Receptors, Type I/metabolism ; Humans ; Macrophages/metabolism ; Signal Transduction |
مستخلص: | Macrophages play crucial roles in many human disease processes. However, obtaining large numbers of primary cells for study is often difficult. We describe 2D and 3D methods for directing human induced pluripotent stem cells (hiPSCs) into macrophages (iMACs). iMACs generated in 2D culture showed functional similarities to human primary monocyte-derived M2-like macrophages, and could be successfully polarized into a M1-like phenotype. Both M1- and M2-like iMACs showed phagocytic activity and reactivity to endogenous or exogenous stimuli. In contrast, iMACs generated by a 3D culture system showed mixed M1- and M2-like functional characteristics. 2D-iMACs from patients with fibrodysplasia ossificans progressiva (FOP), an inherited disease with progressive heterotopic ossification driven by inflammation, showed prolonged inflammatory cytokine production and higher Activin A production after M1-like polarization, resulting in dampened responses to additional LPS stimulation. These results demonstrate a simple and robust way of creating hiPSC-derived M1- and M2-like macrophage lineages, while identifying macrophages as a source of Activin A that may drive heterotopic ossification in FOP. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.) |
التعليقات: | Erratum in: Bone. 2022 May;158:116325. (PMID: 35241401) |
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معلومات مُعتمدة: | R01 AR066735 United States AR NIAMS NIH HHS; T32 AR069516 United States AR NIAMS NIH HHS; R01 AR073015 United States AR NIAMS NIH HHS; UG3 DK120004 United States DK NIDDK NIH HHS; I01 BX002994 United States BX BLRD VA; P30 AR070155 United States AR NIAMS NIH HHS; UH3 DK120004 United States DK NIDDK NIH HHS; P30 AR075055 United States AR NIAMS NIH HHS; R21 AR072778 United States AR NIAMS NIH HHS |
فهرسة مساهمة: | Keywords: Activin A; Cytokines; FOP; Fibrodysplasia ossificans progressiva; Heterotopic ossification; Human induced pluripotent stem cells; Immune activation; Inflammation; Macrophages |
المشرفين على المادة: | EC 2.7.11.30 (ACVR1 protein, human) EC 2.7.11.30 (Activin Receptors, Type I) |
تواريخ الأحداث: | Date Created: 20210726 Date Completed: 20211025 Latest Revision: 20240213 |
رمز التحديث: | 20240213 |
مُعرف محوري في PubMed: | PMC8803261 |
DOI: | 10.1016/j.bone.2021.116129 |
PMID: | 34311122 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1873-2763 |
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DOI: | 10.1016/j.bone.2021.116129 |