Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts
Elucidating the pathways that lead to vasculogenic cells, and being able to identify their progenitors and lineage-restricted cells, is critical to the establishment of human pluripotent stem cell (hPSC) models for vascular diseases and development of vascular therapies. Here, we find that mesoderm-...
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Elsevier
2017-05-01
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Series: | Cell Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717306447 |
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author | Akhilesh Kumar Saritha Sandra D’Souza Oleg V. Moskvin Huishi Toh Bowen Wang Jue Zhang Scott Swanson Lian-Wang Guo James A. Thomson Igor I. Slukvin |
author_facet | Akhilesh Kumar Saritha Sandra D’Souza Oleg V. Moskvin Huishi Toh Bowen Wang Jue Zhang Scott Swanson Lian-Wang Guo James A. Thomson Igor I. Slukvin |
author_sort | Akhilesh Kumar |
collection | DOAJ |
description | Elucidating the pathways that lead to vasculogenic cells, and being able to identify their progenitors and lineage-restricted cells, is critical to the establishment of human pluripotent stem cell (hPSC) models for vascular diseases and development of vascular therapies. Here, we find that mesoderm-derived pericytes (PCs) and smooth muscle cells (SMCs) originate from a clonal mesenchymal progenitor mesenchymoangioblast (MB). In clonogenic cultures, MBs differentiate into primitive PDGFRβ+CD271+CD73− mesenchymal progenitors, which give rise to proliferative PCs, SMCs, and mesenchymal stem/stromal cells. MB-derived PCs can be further specified to CD274+ capillary and DLK1+ arteriolar PCs with a proinflammatory and contractile phenotype, respectively. SMC maturation was induced using a MEK inhibitor. Establishing the vasculogenic lineage tree, along with identification of stage- and lineage-specific markers, provides a platform for interrogating the molecular mechanisms that regulate vasculogenic cell specification and diversification and manufacturing well-defined mural cell populations for vascular engineering and cellular therapies from hPSCs. |
first_indexed | 2024-12-10T19:27:48Z |
format | Article |
id | doaj.art-21f85a4a1154445188b40f5f8dccef6b |
institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-12-10T19:27:48Z |
publishDate | 2017-05-01 |
publisher | Elsevier |
record_format | Article |
series | Cell Reports |
spelling | doaj.art-21f85a4a1154445188b40f5f8dccef6b2022-12-22T01:36:20ZengElsevierCell Reports2211-12472017-05-011991902191610.1016/j.celrep.2017.05.019Specification and Diversification of Pericytes and Smooth Muscle Cells from MesenchymoangioblastsAkhilesh Kumar0Saritha Sandra D’Souza1Oleg V. Moskvin2Huishi Toh3Bowen Wang4Jue Zhang5Scott Swanson6Lian-Wang Guo7James A. Thomson8Igor I. Slukvin9Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USAWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USAWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USANeuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USADepartment of Surgery, University of Wisconsin-Madison, Madison, WI 53792, USAMorgridge Institute for Research, Madison, WI 53707, USAMorgridge Institute for Research, Madison, WI 53707, USADepartment of Surgery, University of Wisconsin-Madison, Madison, WI 53792, USAMorgridge Institute for Research, Madison, WI 53707, USAWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USAElucidating the pathways that lead to vasculogenic cells, and being able to identify their progenitors and lineage-restricted cells, is critical to the establishment of human pluripotent stem cell (hPSC) models for vascular diseases and development of vascular therapies. Here, we find that mesoderm-derived pericytes (PCs) and smooth muscle cells (SMCs) originate from a clonal mesenchymal progenitor mesenchymoangioblast (MB). In clonogenic cultures, MBs differentiate into primitive PDGFRβ+CD271+CD73− mesenchymal progenitors, which give rise to proliferative PCs, SMCs, and mesenchymal stem/stromal cells. MB-derived PCs can be further specified to CD274+ capillary and DLK1+ arteriolar PCs with a proinflammatory and contractile phenotype, respectively. SMC maturation was induced using a MEK inhibitor. Establishing the vasculogenic lineage tree, along with identification of stage- and lineage-specific markers, provides a platform for interrogating the molecular mechanisms that regulate vasculogenic cell specification and diversification and manufacturing well-defined mural cell populations for vascular engineering and cellular therapies from hPSCs.http://www.sciencedirect.com/science/article/pii/S2211124717306447pericytessmooth musclespluripotent stem cellsmesenchymoangioblastdevelopment |
spellingShingle | Akhilesh Kumar Saritha Sandra D’Souza Oleg V. Moskvin Huishi Toh Bowen Wang Jue Zhang Scott Swanson Lian-Wang Guo James A. Thomson Igor I. Slukvin Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts Cell Reports pericytes smooth muscles pluripotent stem cells mesenchymoangioblast development |
title | Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts |
title_full | Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts |
title_fullStr | Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts |
title_full_unstemmed | Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts |
title_short | Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts |
title_sort | specification and diversification of pericytes and smooth muscle cells from mesenchymoangioblasts |
topic | pericytes smooth muscles pluripotent stem cells mesenchymoangioblast development |
url | http://www.sciencedirect.com/science/article/pii/S2211124717306447 |
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