دورية أكاديمية
أعرض في EDS

Directed Differentiation of Human Induced Pluripotent Stem Cells to Heart Valve Cells.

التفاصيل البيبلوغرافية
العنوان: Directed Differentiation of Human Induced Pluripotent Stem Cells to Heart Valve Cells.
المؤلفون: Cai Z; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (Z.C., L.X., Y.X., W.Y.Y., H.C., R.G., X.Q, J.S., W.Q., N.D.).; Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, Fuzhou, China (Z.C.)., Zhu M; Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, Fuzhou, China (Z.C.).; Institute of Maternal and Children Health, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji medical College, Huazhong University of Science & Technology, Hubei, China (M.Z.)., Xu L; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (Z.C., L.X., Y.X., W.Y.Y., H.C., R.G., X.Q, J.S., W.Q., N.D.)., Wang Y; Department of Anesthesiology, Union Hospital, Fujian Medical University, Fuzhou, China (Y.W.)., Xu Y; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (Z.C., L.X., Y.X., W.Y.Y., H.C., R.G., X.Q, J.S., W.Q., N.D.)., Yim WY; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (Z.C., L.X., Y.X., W.Y.Y., H.C., R.G., X.Q, J.S., W.Q., N.D.)., Cao H; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (Z.C., L.X., Y.X., W.Y.Y., H.C., R.G., X.Q, J.S., W.Q., N.D.)., Guo R; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (Z.C., L.X., Y.X., W.Y.Y., H.C., R.G., X.Q, J.S., W.Q., N.D.)., Qiu X; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (Z.C., L.X., Y.X., W.Y.Y., H.C., R.G., X.Q, J.S., W.Q., N.D.)., He X; Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (M.Z., X.H.)., Shi J; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (Z.C., L.X., Y.X., W.Y.Y., H.C., R.G., X.Q, J.S., W.Q., N.D.)., Qiao W; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (Z.C., L.X., Y.X., W.Y.Y., H.C., R.G., X.Q, J.S., W.Q., N.D.)., Dong N; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (Z.C., L.X., Y.X., W.Y.Y., H.C., R.G., X.Q, J.S., W.Q., N.D.).
المصدر: Circulation [Circulation] 2024 Apr 30; Vol. 149 (18), pp. 1435-1456. Date of Electronic Publication: 2024 Feb 15.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0147763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4539 (Electronic) Linking ISSN: 00097322 NLM ISO Abbreviation: Circulation Subsets: MEDLINE
أسماء مطبوعة: Publication: Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: [Dallas, Tex., etc., American Heart Association, etc.]
مواضيع طبية MeSH: Induced Pluripotent Stem Cells*/cytology , Induced Pluripotent Stem Cells*/metabolism , Cell Differentiation* , Heart Valves*/cytology , Heart Valves*/metabolism, Humans ; Cells, Cultured ; Endothelial Cells/metabolism ; Endothelial Cells/cytology ; Signal Transduction
مستخلص: Background: A main obstacle in current valvular heart disease research is the lack of high-quality homogeneous functional heart valve cells. Human induced pluripotent stem cells (hiPSCs)-derived heart valve cells may help with this dilemma. However, there are no well-established protocols to induce hiPSCs to differentiate into functional heart valve cells, and the networks that mediate the differentiation have not been fully elucidated.
Methods: To generate heart valve cells from hiPSCs, we sequentially activated the Wnt, BMP4, VEGF (vascular endothelial growth factor), and NFATc1 signaling pathways using CHIR-99021, BMP4, VEGF-165, and forskolin, respectively. The transcriptional and functional similarity of hiPSC-derived heart valve cells compared with primary heart valve cells were characterized. Longitudinal single-cell RNA sequencing was used to uncover the trajectory, switch genes, pathways, and transcription factors of the differentiation.
Results: An efficient protocol was developed to induce hiPSCs to differentiate into functional hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells. After 6-day differentiation and CD144 magnetic bead sorting, ≈70% CD144 + cells and 30% CD144 - cells were obtained. On the basis of single-cell RNA sequencing data, the CD144 + cells and CD144 - cells were found to be highly similar to primary heart valve endothelial cells and primary heart valve interstitial cells in gene expression profile. Furthermore, CD144 + cells had the typical function of primary heart valve endothelial cells, including tube formation, uptake of low-density lipoprotein, generation of endothelial nitric oxide synthase, and response to shear stress. Meanwhile, CD144 - cells could secret collagen and matrix metalloproteinases, and differentiate into osteogenic or adipogenic lineages like primary heart valve interstitial cells. Therefore, we identified CD144 + cells and CD144 - cells as hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells, respectively. Using single-cell RNA sequencing analysis, we demonstrated that the trajectory of heart valve cell differentiation was consistent with embryonic valve development. We identified the main switch genes (NOTCH1, HEY1, and MEF2C), signaling pathways (TGF-β, Wnt, and NOTCH), and transcription factors (MSX1, SP5, and MECOM) that mediated the differentiation. Finally, we found that hiPSC-derived valve interstitial-like cells might derive from hiPSC-derived valve endothelial-like cells undergoing endocardial-mesenchymal transition.
Conclusions: In summary, this is the first study to report an efficient strategy to generate functional hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells from hiPSCs, as well as to elucidate the differentiation trajectory and transcriptional dynamics of hiPSCs differentiated into heart valve cells.
Competing Interests: Disclosures None.
التعليقات: Comment in: Circulation. 2024 Apr 30;149(18):1457-1460. (PMID: 38683900)
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فهرسة مساهمة: Keywords: cell differentiation; endothelial cells; heart valves; induced pluripotent stem cells; single-cell gene expression analysis
تواريخ الأحداث: Date Created: 20240215 Date Completed: 20240429 Latest Revision: 20240503
رمز التحديث: 20240503
مُعرف محوري في PubMed: PMC11062615
DOI: 10.1161/CIRCULATIONAHA.123.065143
PMID: 38357822
قاعدة البيانات: MEDLINE
الوصف
تدمد:1524-4539
DOI:10.1161/CIRCULATIONAHA.123.065143