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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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2017-05-01
Series:Cell Reports
Subjects:
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.
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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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