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Revisiting Cardiac Cellular Composition
RATIONALE:Accurate knowledge of the cellular composition of the heart is essential to fully understand the changes that occur during pathogenesis and to devise strategies for tissue engineering and regeneration. OBJECTIVE:To examine the relative frequency of cardiac endothelial cells, hematopoietic-...
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| Published in: | Circulation research 2016-02, Vol.118 (3), p.400-409 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Article |
| Language: | English |
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| cites | cdi_FETCH-LOGICAL-c5749-9c930e54eb726f8dd5e8e9309516a845de7d15aa6634c9f59f2b67faf0b084f63 |
| container_end_page | 409 |
| container_issue | 3 |
| container_start_page | 400 |
| container_title | Circulation research |
| container_volume | 118 |
| creator | Pinto, Alexander R Ilinykh, Alexei Ivey, Malina J Kuwabara, Jill T D’Antoni, Michelle L Debuque, Ryan Chandran, Anjana Wang, Lina Arora, Komal Rosenthal, Nadia A Tallquist, Michelle D |
| description | RATIONALE:Accurate knowledge of the cellular composition of the heart is essential to fully understand the changes that occur during pathogenesis and to devise strategies for tissue engineering and regeneration.
OBJECTIVE:To examine the relative frequency of cardiac endothelial cells, hematopoietic-derived cells, and fibroblasts in the mouse and human heart.
METHODS AND RESULTS:Using a combination of genetic tools and cellular markers, we examined the occurrence of the most prominent cell types in the adult mouse heart. Immunohistochemistry revealed that endothelial cells constitute >60%, hematopoietic-derived cells 5% to 10%, and fibroblasts |
| doi_str_mv | 10.1161/CIRCRESAHA.115.307778 |
| format | article |
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OBJECTIVE:To examine the relative frequency of cardiac endothelial cells, hematopoietic-derived cells, and fibroblasts in the mouse and human heart.
METHODS AND RESULTS:Using a combination of genetic tools and cellular markers, we examined the occurrence of the most prominent cell types in the adult mouse heart. Immunohistochemistry revealed that endothelial cells constitute >60%, hematopoietic-derived cells 5% to 10%, and fibroblasts <20% of the nonmyocytes in the heart. A refined cell isolation protocol and an improved flow cytometry approach provided an independent means of determining the relative abundance of nonmyocytes. High-dimensional analysis and unsupervised clustering of cell populations confirmed that endothelial cells are the most abundant cell population. Interestingly, fibroblast numbers are smaller than previously estimated, and 2 commonly assigned fibroblast markers, Sca-1 and CD90, under-represent fibroblast numbers. We also describe an alternative fibroblast surface marker that more accurately identifies the resident cardiac fibroblast population.
CONCLUSIONS:This new perspective on the abundance of different cell types in the heart demonstrates that fibroblasts comprise a relatively minor population. By contrast, endothelial cells constitute the majority of noncardiomyocytes and are likely to play a greater role in physiological function and response to injury than previously appreciated.</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/CIRCRESAHA.115.307778</identifier><identifier>PMID: 26635390</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Adult ; Animals ; Biomarkers - metabolism ; Cell Count ; Cell Differentiation ; Cell Lineage ; Cell Separation - methods ; Endothelial Cells - metabolism ; Female ; Fibroblasts - metabolism ; Flow Cytometry ; Gene Expression Regulation ; Green Fluorescent Proteins - biosynthesis ; Green Fluorescent Proteins - genetics ; Heart ; Hematopoietic Stem Cells - metabolism ; Humans ; Immunohistochemistry ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; Middle Aged ; Phenotype</subject><ispartof>Circulation research, 2016-02, Vol.118 (3), p.400-409</ispartof><rights>2016 American Heart Association, Inc.</rights><rights>2015 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5749-9c930e54eb726f8dd5e8e9309516a845de7d15aa6634c9f59f2b67faf0b084f63</citedby><cites>FETCH-LOGICAL-c5749-9c930e54eb726f8dd5e8e9309516a845de7d15aa6634c9f59f2b67faf0b084f63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,783,787,888,27936,27937</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26635390$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pinto, Alexander R</creatorcontrib><creatorcontrib>Ilinykh, Alexei</creatorcontrib><creatorcontrib>Ivey, Malina J</creatorcontrib><creatorcontrib>Kuwabara, Jill T</creatorcontrib><creatorcontrib>D’Antoni, Michelle L</creatorcontrib><creatorcontrib>Debuque, Ryan</creatorcontrib><creatorcontrib>Chandran, Anjana</creatorcontrib><creatorcontrib>Wang, Lina</creatorcontrib><creatorcontrib>Arora, Komal</creatorcontrib><creatorcontrib>Rosenthal, Nadia A</creatorcontrib><creatorcontrib>Tallquist, Michelle D</creatorcontrib><title>Revisiting Cardiac Cellular Composition</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>RATIONALE:Accurate knowledge of the cellular composition of the heart is essential to fully understand the changes that occur during pathogenesis and to devise strategies for tissue engineering and regeneration.
OBJECTIVE:To examine the relative frequency of cardiac endothelial cells, hematopoietic-derived cells, and fibroblasts in the mouse and human heart.
METHODS AND RESULTS:Using a combination of genetic tools and cellular markers, we examined the occurrence of the most prominent cell types in the adult mouse heart. Immunohistochemistry revealed that endothelial cells constitute >60%, hematopoietic-derived cells 5% to 10%, and fibroblasts <20% of the nonmyocytes in the heart. A refined cell isolation protocol and an improved flow cytometry approach provided an independent means of determining the relative abundance of nonmyocytes. High-dimensional analysis and unsupervised clustering of cell populations confirmed that endothelial cells are the most abundant cell population. Interestingly, fibroblast numbers are smaller than previously estimated, and 2 commonly assigned fibroblast markers, Sca-1 and CD90, under-represent fibroblast numbers. We also describe an alternative fibroblast surface marker that more accurately identifies the resident cardiac fibroblast population.
CONCLUSIONS:This new perspective on the abundance of different cell types in the heart demonstrates that fibroblasts comprise a relatively minor population. By contrast, endothelial cells constitute the majority of noncardiomyocytes and are likely to play a greater role in physiological function and response to injury than previously appreciated.</description><subject>Adult</subject><subject>Animals</subject><subject>Biomarkers - metabolism</subject><subject>Cell Count</subject><subject>Cell Differentiation</subject><subject>Cell Lineage</subject><subject>Cell Separation - methods</subject><subject>Endothelial Cells - metabolism</subject><subject>Female</subject><subject>Fibroblasts - metabolism</subject><subject>Flow Cytometry</subject><subject>Gene Expression Regulation</subject><subject>Green Fluorescent Proteins - biosynthesis</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Heart</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Middle Aged</subject><subject>Phenotype</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNpVUctOwzAQtBAIyuMTQL3BJWX9ji9IVQQUCQmpwNlyEocG0rjYCRV_j6uU12m1u7Mzu7MInWKYYCzwZXY3z-bXj9PZNOZ8QkFKme6gEeaEJYxLvItGAKASSSkcoMMQXgEwo0TtowMiBOVUwQidz-1HHequbl_GmfFlbYpxZpumb4wfZ265cpuma4_RXmWaYE-28Qg931w_ZbPk_uH2LpveJwWXTCWqUBQsZzaXRFRpWXKb2lhSHAuTMl5aWWJuTNRnhaq4qkguZGUqyCFllaBH6GrgXfX50paFbTtvGr3y9dL4T-1Mrf932nqhX9yHZpIxUCQSXGwJvHvvbej0sg5FvMi01vVBYymI4ooQGaF8gBbeheBt9SODQW9M1r8mx5zrweQ4d_Z3x5-pb1cjgA2AtWs668Nb06-t1wtrmm6h41eAAiYJASyAAIdkU1L0C3tHiHQ</recordid><startdate>20160205</startdate><enddate>20160205</enddate><creator>Pinto, Alexander R</creator><creator>Ilinykh, Alexei</creator><creator>Ivey, Malina J</creator><creator>Kuwabara, Jill T</creator><creator>D’Antoni, Michelle L</creator><creator>Debuque, Ryan</creator><creator>Chandran, Anjana</creator><creator>Wang, Lina</creator><creator>Arora, Komal</creator><creator>Rosenthal, Nadia A</creator><creator>Tallquist, Michelle D</creator><general>American Heart Association, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160205</creationdate><title>Revisiting Cardiac Cellular Composition</title><author>Pinto, Alexander R ; Ilinykh, Alexei ; Ivey, Malina J ; Kuwabara, Jill T ; D’Antoni, Michelle L ; Debuque, Ryan ; Chandran, Anjana ; Wang, Lina ; Arora, Komal ; Rosenthal, Nadia A ; Tallquist, Michelle D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5749-9c930e54eb726f8dd5e8e9309516a845de7d15aa6634c9f59f2b67faf0b084f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Biomarkers - metabolism</topic><topic>Cell Count</topic><topic>Cell Differentiation</topic><topic>Cell Lineage</topic><topic>Cell Separation - methods</topic><topic>Endothelial Cells - metabolism</topic><topic>Female</topic><topic>Fibroblasts - metabolism</topic><topic>Flow Cytometry</topic><topic>Gene Expression Regulation</topic><topic>Green Fluorescent Proteins - biosynthesis</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Heart</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Middle Aged</topic><topic>Phenotype</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pinto, Alexander R</creatorcontrib><creatorcontrib>Ilinykh, Alexei</creatorcontrib><creatorcontrib>Ivey, Malina J</creatorcontrib><creatorcontrib>Kuwabara, Jill T</creatorcontrib><creatorcontrib>D’Antoni, Michelle L</creatorcontrib><creatorcontrib>Debuque, Ryan</creatorcontrib><creatorcontrib>Chandran, Anjana</creatorcontrib><creatorcontrib>Wang, Lina</creatorcontrib><creatorcontrib>Arora, Komal</creatorcontrib><creatorcontrib>Rosenthal, Nadia A</creatorcontrib><creatorcontrib>Tallquist, Michelle D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pinto, Alexander R</au><au>Ilinykh, Alexei</au><au>Ivey, Malina J</au><au>Kuwabara, Jill T</au><au>D’Antoni, Michelle L</au><au>Debuque, Ryan</au><au>Chandran, Anjana</au><au>Wang, Lina</au><au>Arora, Komal</au><au>Rosenthal, Nadia A</au><au>Tallquist, Michelle D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Revisiting Cardiac Cellular Composition</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>2016-02-05</date><risdate>2016</risdate><volume>118</volume><issue>3</issue><spage>400</spage><epage>409</epage><pages>400-409</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><abstract>RATIONALE:Accurate knowledge of the cellular composition of the heart is essential to fully understand the changes that occur during pathogenesis and to devise strategies for tissue engineering and regeneration.
OBJECTIVE:To examine the relative frequency of cardiac endothelial cells, hematopoietic-derived cells, and fibroblasts in the mouse and human heart.
METHODS AND RESULTS:Using a combination of genetic tools and cellular markers, we examined the occurrence of the most prominent cell types in the adult mouse heart. Immunohistochemistry revealed that endothelial cells constitute >60%, hematopoietic-derived cells 5% to 10%, and fibroblasts <20% of the nonmyocytes in the heart. A refined cell isolation protocol and an improved flow cytometry approach provided an independent means of determining the relative abundance of nonmyocytes. High-dimensional analysis and unsupervised clustering of cell populations confirmed that endothelial cells are the most abundant cell population. Interestingly, fibroblast numbers are smaller than previously estimated, and 2 commonly assigned fibroblast markers, Sca-1 and CD90, under-represent fibroblast numbers. We also describe an alternative fibroblast surface marker that more accurately identifies the resident cardiac fibroblast population.
CONCLUSIONS:This new perspective on the abundance of different cell types in the heart demonstrates that fibroblasts comprise a relatively minor population. By contrast, endothelial cells constitute the majority of noncardiomyocytes and are likely to play a greater role in physiological function and response to injury than previously appreciated.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>26635390</pmid><doi>10.1161/CIRCRESAHA.115.307778</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation research, 2016-02, Vol.118 (3), p.400-409 |
| issn | 0009-7330 1524-4571 |
| language | eng |
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| source | Science Journals (Open access) |
| subjects | Adult Animals Biomarkers - metabolism Cell Count Cell Differentiation Cell Lineage Cell Separation - methods Endothelial Cells - metabolism Female Fibroblasts - metabolism Flow Cytometry Gene Expression Regulation Green Fluorescent Proteins - biosynthesis Green Fluorescent Proteins - genetics Heart Hematopoietic Stem Cells - metabolism Humans Immunohistochemistry Male Mice, Inbred C57BL Mice, Transgenic Middle Aged Phenotype |
| title | Revisiting Cardiac Cellular Composition |
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