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  1. Article ; Online: A new resource for human coronary vessel development.

    Phansalkar, Ragini / Red-Horse, Kristy

    Cardiovascular research

    2022  Volume 118, Issue 14, Page(s) 2875–2876

    MeSH term(s) Humans ; Coronary Vessels/diagnostic imaging ; Heart ; Angioplasty, Balloon, Coronary ; Endothelium ; Gene Expression ; MDS1 and EVI1 Complex Locus Protein
    Chemical Substances MECOM protein, human ; MDS1 and EVI1 Complex Locus Protein
    Language English
    Publishing date 2022-06-26
    Publishing country England
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvac094
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  2. Article ; Online: Vascular endothelial cell development and diversity.

    Trimm, Emily / Red-Horse, Kristy

    Nature reviews. Cardiology

    2022  Volume 20, Issue 3, Page(s) 197–210

    Abstract: Vascular endothelial cells form the inner layer of blood vessels where they have a key role in the development and maintenance of the functional circulatory system and provide paracrine support to surrounding non-vascular cells. Technical advances in the ...

    Abstract Vascular endothelial cells form the inner layer of blood vessels where they have a key role in the development and maintenance of the functional circulatory system and provide paracrine support to surrounding non-vascular cells. Technical advances in the past 5 years in single-cell genomics and in in vivo genetic labelling have facilitated greater insights into endothelial cell development, plasticity and heterogeneity. These advances have also contributed to a new understanding of the timing of endothelial cell subtype differentiation and its relationship to the cell cycle. Identification of novel tissue-specific gene expression patterns in endothelial cells has led to the discovery of crucial signalling pathways and new interactions with other cell types that have key roles in both tissue maintenance and disease pathology. In this Review, we describe the latest findings in vascular endothelial cell development and diversity, which are often supported by large-scale, single-cell studies, and discuss the implications of these findings for vascular medicine. In addition, we highlight how techniques such as single-cell multimodal omics, which have become increasingly sophisticated over the past 2 years, are being utilized to study normal vascular physiology as well as functional perturbations in disease.
    MeSH term(s) Humans ; Endothelial Cells/physiology ; Cell Differentiation ; Signal Transduction
    Language English
    Publishing date 2022-10-05
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2490375-9
    ISSN 1759-5010 ; 1759-5002
    ISSN (online) 1759-5010
    ISSN 1759-5002
    DOI 10.1038/s41569-022-00770-1
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  3. Article ; Online: New Research Is Shining Light on How Collateral Arteries Form in the Heart: a Future Therapeutic Direction?

    Red-Horse, Kristy / Das, Soumyashree

    Current cardiology reports

    2021  Volume 23, Issue 4, Page(s) 30

    Abstract: Purpose of review: Collateral arteries create artery-artery anastomoses that could serve as natural bypasses that in the heart could relieve the various complications of ischemia heart disease. Recent work using animal models have begun to reveal ... ...

    Abstract Purpose of review: Collateral arteries create artery-artery anastomoses that could serve as natural bypasses that in the heart could relieve the various complications of ischemia heart disease. Recent work using animal models have begun to reveal details of how coronary collateral arteries form.
    Recent findings: Mouse genetics has been used to study the cellular and molecular mechanisms of collateral artery development. Collateral arteries are not pre-existing in the mouse heart, and only form in response to injury. Myocardial infarction creates tissue hypoxia that triggers the expression of growth factors and chemokines that guide collaterogenesis. Collateral development is more robust in neonatal hearts when compared with adults, and contributes to neonatal heart regeneration. The identification of signaling pathways and cellular responses underlying coronary collateral artery development suggests potential translational strategies. Continued investigation into this subject could lead to the identification of targetable pathways that induce collateral arteries for cardiac revascularization.
    MeSH term(s) Animals ; Collateral Circulation ; Coronary Artery Disease ; Heart ; Humans ; Mice ; Neovascularization, Physiologic
    Language English
    Publishing date 2021-03-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2055373-0
    ISSN 1534-3170 ; 1523-3782
    ISSN (online) 1534-3170
    ISSN 1523-3782
    DOI 10.1007/s11886-021-01460-z
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  4. Article ; Online: Techniques converge to map the developing human heart at single-cell level.

    Phansalkar, Ragini / Red-Horse, Kristy

    Nature

    2020  Volume 577, Issue 7792, Page(s) 629–630

    MeSH term(s) Gene Expression ; Heart ; Humans ; Single-Cell Analysis
    Language English
    Publishing date 2020-01-28
    Publishing country England
    Document type News ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-020-00151-z
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  5. Article ; Online: Enhancing cardiovascular research with whole-organ imaging.

    Rios Coronado, Pamela E / Red-Horse, Kristy

    Current opinion in hematology

    2021  Volume 28, Issue 3, Page(s) 214–220

    Abstract: Purpose of review: There have been tremendous advances in the tools available for surveying blood vessels within whole organs and tissues. Here, we summarize some of the recent developments in methods for immunolabeling and imaging whole organs and ... ...

    Abstract Purpose of review: There have been tremendous advances in the tools available for surveying blood vessels within whole organs and tissues. Here, we summarize some of the recent developments in methods for immunolabeling and imaging whole organs and provide a protocol optimized for the heart.
    Recent findings: Multiple protocols have been established for chemically clearing large organs and variations are compatible with cell type-specific labeling. Heart tissue can be successfully cleared to reveal the three-dimensional structure of the entire coronary vasculature in neonatal and adult mice. Obtaining vascular reconstructions requires exceptionally large imaging files and new computational methods to process the data for accurate vascular quantifications. This is a continually advancing field that has revolutionized our ability to acquire data on larger samples as a faster rate.
    Summary: Historically, cardiovascular research has relied heavily on histological analyses that use tissue sections, which usually sample cellular phenotypes in small regions and lack information on whole tissue-level organization. This approach can be modified to survey whole organs but image acquisition and analysis time can become unreasonable. In recent years, whole-organ immunolabeling and clearing methods have emerged as a workable solution, and new microscopy modalities, such as light-sheet microscopy, significantly improve image acquisition times. These innovations make studying the vasculature in the context of the whole organ widely available and promise to reveal fascinating new cellular behaviors in adult tissues and during repair.
    MeSH term(s) Animals ; Cardiovascular Physiological Phenomena ; Cardiovascular System/anatomy & histology ; Cardiovascular System/diagnostic imaging ; Cardiovascular System/metabolism ; Computational Biology/methods ; Diagnostic Imaging/methods ; Fluorescent Antibody Technique ; Humans ; Imaging, Three-Dimensional/methods ; Mice ; Molecular Imaging/methods ; Organ Specificity ; Research
    Language English
    Publishing date 2021-03-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1153887-9
    ISSN 1531-7048 ; 1065-6251
    ISSN (online) 1531-7048
    ISSN 1065-6251
    DOI 10.1097/MOH.0000000000000655
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  6. Article ; Online: Cellular plasticity in cardiovascular development and disease.

    Das, Soumyashree / Red-Horse, Kristy

    Developmental dynamics : an official publication of the American Association of Anatomists

    2017  Volume 246, Issue 4, Page(s) 328–335

    Abstract: Knowledge on cellular differentiation pathways is critical to understanding organ development, homeostasis, and disease. Studying cell differentiation and cell fate restrictions in these contexts can be done through lineage tracing experiments, which ... ...

    Abstract Knowledge on cellular differentiation pathways is critical to understanding organ development, homeostasis, and disease. Studying cell differentiation and cell fate restrictions in these contexts can be done through lineage tracing experiments, which entail permanent labeling of a cell and all its progeny. Recent lineage experiments within the cardiovascular system have uncovered unexpected findings on cellular origins during organogenesis and cell plasticity during disease. For example, there is increasing evidence that multiple progenitor sources exist for a single cell type, and that cells have remarkable expansive capacities under disease settings. Here, we summarize some recent findings in the cardiovascular system and highlight where there is evidence that the underlying concepts are a widespread phenomenon used by other organ systems. Developmental Dynamics 246:328-335, 2017. © 2016 Wiley Periodicals, Inc.
    Language English
    Publishing date 2017-04
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1102541-4
    ISSN 1097-0177 ; 1058-8388
    ISSN (online) 1097-0177
    ISSN 1058-8388
    DOI 10.1002/dvdy.24486
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  7. Article ; Online: Eph-ephrin signaling couples endothelial cell sorting and arterial specification.

    Stewen, Jonas / Kruse, Kai / Godoi-Filip, Anca T / Zenia / Jeong, Hyun-Woo / Adams, Susanne / Berkenfeld, Frank / Stehling, Martin / Red-Horse, Kristy / Adams, Ralf H / Pitulescu, Mara E

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2539

    Abstract: Cell segregation allows the compartmentalization of cells with similar fates during morphogenesis, which can be enhanced by cell fate plasticity in response to local molecular and biomechanical cues. Endothelial tip cells in the growing retina, which ... ...

    Abstract Cell segregation allows the compartmentalization of cells with similar fates during morphogenesis, which can be enhanced by cell fate plasticity in response to local molecular and biomechanical cues. Endothelial tip cells in the growing retina, which lead vessel sprouts, give rise to arterial endothelial cells and thereby mediate arterial growth. Here, we have combined cell type-specific and inducible mouse genetics, flow experiments in vitro, single-cell RNA sequencing and biochemistry to show that the balance between ephrin-B2 and its receptor EphB4 is critical for arterial specification, cell sorting and arteriovenous patterning. At the molecular level, elevated ephrin-B2 function after loss of EphB4 enhances signaling responses by the Notch pathway, VEGF and the transcription factor Dach1, which is influenced by endothelial shear stress. Our findings reveal how Eph-ephrin interactions integrate cell segregation and arteriovenous specification in the vasculature, which has potential relevance for human vascular malformations caused by EPHB4 mutations.
    MeSH term(s) Mice ; Humans ; Animals ; Endothelial Cells/metabolism ; Ephrins ; Ephrin-B2/genetics ; Ephrin-B2/metabolism ; Arteries/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism ; Cell Separation ; Receptor, EphB4/genetics ; Receptor, EphB4/metabolism
    Chemical Substances Ephrins ; Ephrin-B2 ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Receptor, EphB4 (EC 2.7.10.1)
    Language English
    Publishing date 2024-04-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-46300-0
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  8. Article ; Online: Veins and Arteries Build Hierarchical Branching Patterns Differently: Bottom-Up versus Top-Down.

    Red-Horse, Kristy / Siekmann, Arndt F

    BioEssays : news and reviews in molecular, cellular and developmental biology

    2019  Volume 41, Issue 3, Page(s) e1800198

    Abstract: A tree-like hierarchical branching structure is present in many biological systems, such as the kidney, lung, mammary gland, and blood vessels. Most of these organs form through branching morphogenesis, where outward growth results in smaller and smaller ...

    Abstract A tree-like hierarchical branching structure is present in many biological systems, such as the kidney, lung, mammary gland, and blood vessels. Most of these organs form through branching morphogenesis, where outward growth results in smaller and smaller branches. However, the blood vasculature is unique in that it exists as two trees (arterial and venous) connected at their tips. Obtaining this organization might therefore require unique developmental mechanisms. As reviewed here, recent data indicate that arterial trees often form in reverse order. Accordingly, initial arterial endothelial cell differentiation occurs outside of arterial vessels. These pre-artery cells then build trees by following a migratory path from smaller into larger arteries, a process guided by the forces imparted by blood flow. Thus, in comparison to other branched organs, arteries can obtain their structure through inward growth and coalescence. Here, new information on the underlying mechanisms is discussed, and how defects can lead to pathologies, such as hypoplastic arteries and arteriovenous malformations.
    MeSH term(s) Animals ; Arteries/embryology ; Arteries/growth & development ; Cell Differentiation/physiology ; Cell Movement ; Cell Plasticity ; Epithelial Cells/physiology ; Humans ; Mice ; Morphogenesis ; Neovascularization, Physiologic ; Receptors, CXCR4/metabolism ; Receptors, Notch/metabolism ; Transforming Growth Factor beta/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Veins/embryology ; Veins/growth & development ; Zebrafish
    Chemical Substances Receptors, CXCR4 ; Receptors, Notch ; Transforming Growth Factor beta ; Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2019-02-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.201800198
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  9. Article ; Online: Endothelial ontogeny and the establishment of vascular heterogeneity.

    Stone, Oliver A / Zhou, Bin / Red-Horse, Kristy / Stainier, Didier Y R

    BioEssays : news and reviews in molecular, cellular and developmental biology

    2021  Volume 43, Issue 7, Page(s) e2100036

    Abstract: The establishment of distinct cellular identities was pivotal during the evolution of Metazoa, enabling the emergence of an array of specialized tissues with different functions. In most animals including vertebrates, cell specialization occurs in ... ...

    Abstract The establishment of distinct cellular identities was pivotal during the evolution of Metazoa, enabling the emergence of an array of specialized tissues with different functions. In most animals including vertebrates, cell specialization occurs in response to a combination of intrinsic (e.g., cellular ontogeny) and extrinsic (e.g., local environment) factors that drive the acquisition of unique characteristics at the single-cell level. The first functional organ system to form in vertebrates is the cardiovascular system, which is lined by a network of endothelial cells whose organ-specific characteristics have long been recognized. Recent genetic analyses at the single-cell level have revealed that heterogeneity exists not only at the organ level but also between neighboring endothelial cells. Thus, how endothelial heterogeneity is established has become a key question in vascular biology. Drawing upon evidence from multiple organ systems, here we will discuss the role that lineage history may play in establishing endothelial heterogeneity.
    MeSH term(s) Animals ; Cell Proliferation ; Endothelial Cells ; Vertebrates/genetics
    Language English
    Publishing date 2021-07-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.202100036
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  10. Article ; Online: APJ+ cells in the SHF contribute to the cells of aorta and pulmonary trunk through APJ signaling.

    Baral, Kamal / D'amato, Gaetano / Kuschel, Bryce / Bogan, Frank / Jones, Brendan W / Large, Colton L / Whatley, Jeffery D / Red-Horse, Kristy / Sharma, Bikram

    Developmental biology

    2023  Volume 498, Page(s) 77–86

    Abstract: Outflow tract (OFT) develops from cardiac progenitor cells in the second heart field (SHF) domain. APJ, a G-Protein Coupled Receptor, is expressed by cardiac progenitors in the SHF. By lineage tracing APJ+SHF cells, we show that these cardiac progenitors ...

    Abstract Outflow tract (OFT) develops from cardiac progenitor cells in the second heart field (SHF) domain. APJ, a G-Protein Coupled Receptor, is expressed by cardiac progenitors in the SHF. By lineage tracing APJ+SHF cells, we show that these cardiac progenitors contribute to the cells of OFT, which eventually give rise to aorta and pulmonary trunk/artery upon its morphogenesis. Furthermore, we show that early APJ ​+ ​cells give rise to both aorta and pulmonary cells but late APJ ​+ ​cells predominantly give rise to pulmonary cells. APJ is expressed by the outflow tract progenitors in the SHF but its role is unclear. We performed knockout studies to determine the role of APJ in SHF cell proliferation and survival. Our data suggested that APJ knockout in the SHF reduced the proliferation of SHF progenitors, while there was no significant impact on survival. In addition, we show that ectopic overexpression of WNT in these cells disrupted aorta and pulmonary morphogenesis from OFT. Overall, our study has identified APJ ​+ ​progenitor population within the SHF that give rise to aorta and pulmonary trunk/artery cells. Furthermore, we show that APJ signaling stimulates proliferation of these cells in the SHF.
    MeSH term(s) Heart ; Signal Transduction ; Stem Cells ; Pulmonary Artery ; Aorta ; Myocardium ; Gene Expression Regulation, Developmental
    Language English
    Publishing date 2023-04-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1114-9
    ISSN 1095-564X ; 0012-1606
    ISSN (online) 1095-564X
    ISSN 0012-1606
    DOI 10.1016/j.ydbio.2023.04.003
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