Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts

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

doi:10.1016/j.celrep.2017.05.019

Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts

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

Research output: Contribution to journal › Article › peer-review

165 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1902-1916
Number of pages	15
Journal	Cell reports
Volume	19
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2017.05.019 https://doi.org/10.1016/j.celrep.2017.05.019
State	Published - May 2017
Externally published	Yes

Bibliographical note

Funding Information:
We thank Toru Nakano for providing OP9 cells and Matt Raymond for editorial assistance. This work was supported by funds from the NIH (U01HL099773, P01 GM081629, and P51 OD011106) and The Charlotte Geyer Foundation. I.I.S. is a founding shareholder and consultant for Cynata.

Publisher Copyright:
© 2017 The Author(s)

Keywords

development
mesenchymoangioblast
pericytes
pluripotent stem cells
smooth muscles

PubMed: MeSH publication types

Journal Article

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{8644bdc52873464cb2b1f49d459a24a9,

title = "Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts",

abstract = "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.",

keywords = "development, mesenchymoangioblast, pericytes, pluripotent stem cells, smooth muscles",

author = "Akhilesh Kumar and D'Souza, \{Saritha Sandra\} and Moskvin, \{Oleg V.\} and Huishi Toh and Bowen Wang and Jue Zhang and Scott Swanson and Guo, \{Lian Wang\} and Thomson, \{James A.\} and Slukvin, \{Igor I.\}",

note = "Funding Information: We thank Toru Nakano for providing OP9 cells and Matt Raymond for editorial assistance. This work was supported by funds from the NIH (U01HL099773, P01 GM081629, and P51 OD011106) and The Charlotte Geyer Foundation. I.I.S. is a founding shareholder and consultant for Cynata. Publisher Copyright: {\textcopyright} 2017 The Author(s)",

year = "2017",

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doi = "10.1016/j.celrep.2017.05.019",

language = "English (US)",

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AU - Kumar, Akhilesh

AU - D'Souza, Saritha Sandra

AU - Moskvin, Oleg V.

AU - Toh, Huishi

AU - Wang, Bowen

AU - Zhang, Jue

AU - Swanson, Scott

AU - Guo, Lian Wang

AU - Thomson, James A.

AU - Slukvin, Igor I.

N1 - Funding Information: We thank Toru Nakano for providing OP9 cells and Matt Raymond for editorial assistance. This work was supported by funds from the NIH (U01HL099773, P01 GM081629, and P51 OD011106) and The Charlotte Geyer Foundation. I.I.S. is a founding shareholder and consultant for Cynata. Publisher Copyright: © 2017 The Author(s)

PY - 2017/5

Y1 - 2017/5

N2 - 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.

AB - 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.

KW - development

KW - mesenchymoangioblast

KW - pericytes

KW - pluripotent stem cells

KW - smooth muscles

UR - http://europepmc.org/abstract/med/28564607

U2 - 10.1016/j.celrep.2017.05.019

DO - 10.1016/j.celrep.2017.05.019

M3 - Article

C2 - 28564607

SN - 2211-1247

VL - 19

SP - 1902

EP - 1916

JO - Cell reports

JF - Cell reports

IS - 9

ER -

Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts

Abstract

Bibliographical note

Keywords

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UN SDGs

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