Pericytes are progenitors for coronary artery smooth muscle
Epicardial cells on the heart’s surface give rise to coronary artery smooth muscle cells (caSMCs) located deep in the myocardium. However, the differentiation steps between epicardial cells and caSMCs are unknown as are the final maturation signals at coronary arteries. Here, we use clonal analysis...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2015-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/10036 |
| _version_ | 1818019151401189376 |
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| author | Katharina S Volz Andrew H Jacobs Heidi I Chen Aruna Poduri Andrew S McKay Daniel P Riordan Natalie Kofler Jan Kitajewski Irving Weissman Kristy Red-Horse |
| author_facet | Katharina S Volz Andrew H Jacobs Heidi I Chen Aruna Poduri Andrew S McKay Daniel P Riordan Natalie Kofler Jan Kitajewski Irving Weissman Kristy Red-Horse |
| author_sort | Katharina S Volz |
| collection | DOAJ |
| description | Epicardial cells on the heart’s surface give rise to coronary artery smooth muscle cells (caSMCs) located deep in the myocardium. However, the differentiation steps between epicardial cells and caSMCs are unknown as are the final maturation signals at coronary arteries. Here, we use clonal analysis and lineage tracing to show that caSMCs derive from pericytes, mural cells associated with microvessels, and that these cells are present in adults. During development following the onset of blood flow, pericytes at arterial remodeling sites upregulate Notch3 while endothelial cells express Jagged-1. Deletion of Notch3 disrupts caSMC differentiation. Our data support a model wherein epicardial-derived pericytes populate the entire coronary microvasculature, but differentiate into caSMCs at arterial remodeling zones in response to Notch signaling. Our data are the first demonstration that pericytes are progenitors for smooth muscle, and their presence in adult hearts reveals a new potential cell type for targeting during cardiovascular disease. |
| first_indexed | 2024-04-14T07:48:34Z |
| format | Article |
| id | doaj.art-122633ec49124bdf855c84990fcae4be |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:48:34Z |
| publishDate | 2015-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-122633ec49124bdf855c84990fcae4be2022-12-22T02:05:15ZengeLife Sciences Publications LtdeLife2050-084X2015-10-01410.7554/eLife.10036Pericytes are progenitors for coronary artery smooth muscleKatharina S Volz0Andrew H Jacobs1Heidi I Chen2Aruna Poduri3Andrew S McKay4Daniel P Riordan5Natalie Kofler6Jan Kitajewski7Irving Weissman8Kristy Red-Horse9Stem Cell and Regenerative Medicine PhD Program, Stanford School of Medicine, Stanford, United States; Department of Biological Sciences, Stanford University, Stanford, United States; Institute for Stem Cell and Regenerative Medicine, Stanford School of Medicine, Ludwig Center, Stanford, United StatesDepartment of Biological Sciences, Stanford University, Stanford, United StatesDepartment of Biological Sciences, Stanford University, Stanford, United StatesDepartment of Biological Sciences, Stanford University, Stanford, United StatesDepartment of Biological Sciences, Stanford University, Stanford, United StatesDepartment of Biochemistry, Stanford School of Medicine, Stanford, United StatesColumbia University Medical Center, New York, United StatesColumbia University Medical Center, New York, United StatesInstitute for Stem Cell and Regenerative Medicine, Stanford School of Medicine, Ludwig Center, Stanford, United States; Ludwig Center for Cancer Stem Cell Biology and Medicine at Stanford University, Stanford, United StatesDepartment of Biological Sciences, Stanford University, Stanford, United StatesEpicardial cells on the heart’s surface give rise to coronary artery smooth muscle cells (caSMCs) located deep in the myocardium. However, the differentiation steps between epicardial cells and caSMCs are unknown as are the final maturation signals at coronary arteries. Here, we use clonal analysis and lineage tracing to show that caSMCs derive from pericytes, mural cells associated with microvessels, and that these cells are present in adults. During development following the onset of blood flow, pericytes at arterial remodeling sites upregulate Notch3 while endothelial cells express Jagged-1. Deletion of Notch3 disrupts caSMC differentiation. Our data support a model wherein epicardial-derived pericytes populate the entire coronary microvasculature, but differentiate into caSMCs at arterial remodeling zones in response to Notch signaling. Our data are the first demonstration that pericytes are progenitors for smooth muscle, and their presence in adult hearts reveals a new potential cell type for targeting during cardiovascular disease.https://elifesciences.org/articles/10036cardiovascular developmentvascular smooth muscleNotch signaling |
| spellingShingle | Katharina S Volz Andrew H Jacobs Heidi I Chen Aruna Poduri Andrew S McKay Daniel P Riordan Natalie Kofler Jan Kitajewski Irving Weissman Kristy Red-Horse Pericytes are progenitors for coronary artery smooth muscle eLife cardiovascular development vascular smooth muscle Notch signaling |
| title | Pericytes are progenitors for coronary artery smooth muscle |
| title_full | Pericytes are progenitors for coronary artery smooth muscle |
| title_fullStr | Pericytes are progenitors for coronary artery smooth muscle |
| title_full_unstemmed | Pericytes are progenitors for coronary artery smooth muscle |
| title_short | Pericytes are progenitors for coronary artery smooth muscle |
| title_sort | pericytes are progenitors for coronary artery smooth muscle |
| topic | cardiovascular development vascular smooth muscle Notch signaling |
| url | https://elifesciences.org/articles/10036 |
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