Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Progenitors via Small-Molecule Activation of WNT Signaling
Human pluripotent stem cell (hPSC)-derived endothelial cells and their progenitors may provide the means for vascularization of tissue-engineered constructs and can serve as models to study vascular development and disease. Here, we report a method to efficiently produce endothelial cells from hPSCs...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-11-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671114002902 |
| _version_ | 1818950611477987328 |
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| author | Xiaojun Lian Xiaoping Bao Abraham Al-Ahmad Jialu Liu Yue Wu Wentao Dong Kaitlin K. Dunn Eric V. Shusta Sean P. Palecek |
| author_facet | Xiaojun Lian Xiaoping Bao Abraham Al-Ahmad Jialu Liu Yue Wu Wentao Dong Kaitlin K. Dunn Eric V. Shusta Sean P. Palecek |
| author_sort | Xiaojun Lian |
| collection | DOAJ |
| description | Human pluripotent stem cell (hPSC)-derived endothelial cells and their progenitors may provide the means for vascularization of tissue-engineered constructs and can serve as models to study vascular development and disease. Here, we report a method to efficiently produce endothelial cells from hPSCs via GSK3 inhibition and culture in defined media to direct hPSC differentiation to CD34+CD31+ endothelial progenitors. Exogenous vascular endothelial growth factor (VEGF) treatment was dispensable, and endothelial progenitor differentiation was β-catenin dependent. Furthermore, by clonal analysis, we showed that CD34+CD31+CD117+TIE-2+ endothelial progenitors were multipotent, capable of differentiating into calponin-expressing smooth muscle cells and CD31+CD144+vWF+I-CAM1+ endothelial cells. These endothelial cells were capable of 20 population doublings, formed tube-like structures, imported acetylated low-density lipoprotein, and maintained a dynamic barrier function. This study provides a rapid and efficient method for production of hPSC-derived endothelial progenitors and endothelial cells and identifies WNT/β-catenin signaling as a primary regulator for generating vascular cells from hPSCs. |
| first_indexed | 2024-12-20T09:21:20Z |
| format | Article |
| id | doaj.art-b677258a9e584a88be1056fb2d83dda8 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-20T09:21:20Z |
| publishDate | 2014-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-b677258a9e584a88be1056fb2d83dda82022-12-21T19:45:17ZengElsevierStem Cell Reports2213-67112014-11-013580481610.1016/j.stemcr.2014.09.005Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Progenitors via Small-Molecule Activation of WNT SignalingXiaojun Lian0Xiaoping Bao1Abraham Al-Ahmad2Jialu Liu3Yue Wu4Wentao Dong5Kaitlin K. Dunn6Eric V. Shusta7Sean P. Palecek8Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USAHuman pluripotent stem cell (hPSC)-derived endothelial cells and their progenitors may provide the means for vascularization of tissue-engineered constructs and can serve as models to study vascular development and disease. Here, we report a method to efficiently produce endothelial cells from hPSCs via GSK3 inhibition and culture in defined media to direct hPSC differentiation to CD34+CD31+ endothelial progenitors. Exogenous vascular endothelial growth factor (VEGF) treatment was dispensable, and endothelial progenitor differentiation was β-catenin dependent. Furthermore, by clonal analysis, we showed that CD34+CD31+CD117+TIE-2+ endothelial progenitors were multipotent, capable of differentiating into calponin-expressing smooth muscle cells and CD31+CD144+vWF+I-CAM1+ endothelial cells. These endothelial cells were capable of 20 population doublings, formed tube-like structures, imported acetylated low-density lipoprotein, and maintained a dynamic barrier function. This study provides a rapid and efficient method for production of hPSC-derived endothelial progenitors and endothelial cells and identifies WNT/β-catenin signaling as a primary regulator for generating vascular cells from hPSCs.http://www.sciencedirect.com/science/article/pii/S2213671114002902 |
| spellingShingle | Xiaojun Lian Xiaoping Bao Abraham Al-Ahmad Jialu Liu Yue Wu Wentao Dong Kaitlin K. Dunn Eric V. Shusta Sean P. Palecek Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Progenitors via Small-Molecule Activation of WNT Signaling Stem Cell Reports |
| title | Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Progenitors via Small-Molecule Activation of WNT Signaling |
| title_full | Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Progenitors via Small-Molecule Activation of WNT Signaling |
| title_fullStr | Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Progenitors via Small-Molecule Activation of WNT Signaling |
| title_full_unstemmed | Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Progenitors via Small-Molecule Activation of WNT Signaling |
| title_short | Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Progenitors via Small-Molecule Activation of WNT Signaling |
| title_sort | efficient differentiation of human pluripotent stem cells to endothelial progenitors via small molecule activation of wnt signaling |
| url | http://www.sciencedirect.com/science/article/pii/S2213671114002902 |
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