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  1. Article ; Online: Endothelial Cell Differentiation and Hemogenic Specification.

    Aragon, Jordon W / Hirschi, Karen K

    Cold Spring Harbor perspectives in medicine

    2022  Volume 12, Issue 7

    Abstract: Formation of the vasculature is a critical step within the developing embryo and its disruption causes early embryonic lethality. This complex process is driven by a cascade of signaling events that controls differentiation of mesodermal progenitors into ...

    Abstract Formation of the vasculature is a critical step within the developing embryo and its disruption causes early embryonic lethality. This complex process is driven by a cascade of signaling events that controls differentiation of mesodermal progenitors into primordial endothelial cells and their further specification into distinct subtypes (arterial, venous, hemogenic) that are needed to generate a blood circulatory network. Hemogenic endothelial cells give rise to hematopoietic stem and progenitor cells that generate all blood cells in the body during embryogenesis and postnatally. We focus our discussion on the regulation of endothelial cell differentiation, and subsequent hemogenic specification, and highlight many of the signaling pathways involved in these processes, which are conserved across vertebrates. Gaining a better understanding of the regulation of these processes will yield insights needed to optimize the treatment of vascular and hematopoietic disease and generate human stem cell-derived vascular and hematopoietic cells for tissue engineering and regenerative medicine.
    MeSH term(s) Animals ; Cell Differentiation/physiology ; Hemangioblasts ; Hematopoiesis/physiology ; Hematopoietic Stem Cells/metabolism ; Humans ; Signal Transduction/physiology
    Language English
    Publishing date 2022-07-29
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ISSN 2157-1422
    ISSN (online) 2157-1422
    DOI 10.1101/cshperspect.a041164
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Tissue-Resident Macrophage Development and Function.

    Wu, Yinyu / Hirschi, Karen K

    Frontiers in cell and developmental biology

    2021  Volume 8, Page(s) 617879

    Abstract: Tissue-resident macrophages have been associated with important and diverse biological processes such as native immunity, tissue homeostasis and angiogenesis during development and postnatally. Thus, it is critical to understand the origins and functions ...

    Abstract Tissue-resident macrophages have been associated with important and diverse biological processes such as native immunity, tissue homeostasis and angiogenesis during development and postnatally. Thus, it is critical to understand the origins and functions of tissue-resident macrophages, as well as mechanisms underlying their regulation. It is now well accepted that murine macrophages are produced during three consecutive waves of hematopoietic development. The first wave of macrophage formation takes place during primitive hematopoiesis, which occurs in the yolk sac, and gives rise to primitive erythroid, megakaryocyte and macrophage progenitors. These "primitive" macrophage progenitors ultimately give rise to microglia in the adult brain. The second wave, which also occurs in the yolk sac, generates multipotent erythro-myeloid progenitors (EMP), which give rise to tissue-resident macrophages. Tissue-resident macrophages derived from EMP reside in diverse niches of different tissues except the brain, and demonstrate tissue-specific functions therein. The third wave of macrophages derives from hematopoietic stem cells (HSC) that are formed in the aorta-gonad-mesonephros (AGM) region of the embryo and migrate to, and colonize, the fetal liver. These HSC-derived macrophages are a long-lived pool that will last throughout adulthood. In this review, we discuss the developmental origins of tissue-resident macrophages, their molecular regulation in specific tissues, and their impact on embryonic development and postnatal homeostasis.
    Language English
    Publishing date 2021-01-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2020.617879
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Understanding neural stem cell regulation

    Genet, Nafiisha / Hirschi, Karen K

    Regenerative medicine

    2021  Volume 16, Issue 9, Page(s) 861–870

    Abstract: The use of neural stem cell (NSC) therapy for the treatment of stroke patients is successfully paving its way into advanced phases of large-scale clinical trials. To understand how to optimize NSC therapeutic approaches, it is fundamental to decipher the ...

    Abstract The use of neural stem cell (NSC) therapy for the treatment of stroke patients is successfully paving its way into advanced phases of large-scale clinical trials. To understand how to optimize NSC therapeutic approaches, it is fundamental to decipher the crosstalk between NSC and other cells that comprise the NSC microenvironment (niche) and regulate their function,
    MeSH term(s) Endothelial Cells ; Humans ; Neural Stem Cells ; Neurogenesis ; Stem Cell Niche ; Stem Cell Transplantation ; Stroke/therapy
    Language English
    Publishing date 2021-09-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2274500-2
    ISSN 1746-076X ; 1746-0751
    ISSN (online) 1746-076X
    ISSN 1746-0751
    DOI 10.2217/rme-2021-0022
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  4. Article ; Online: MicroRNA-223 limits murine hemogenic endothelial cell specification and myelopoiesis.

    Wu, Yinyu / Paila, Umadevi / Genet, Gael / Hirschi, Karen K

    Developmental cell

    2023  Volume 58, Issue 14, Page(s) 1237–1249.e5

    Abstract: Embryonic definitive hematopoiesis generates hematopoietic stem and progenitor cells (HSPCs) that are essential for the establishment and maintenance of the adult blood system. This process requires the specification of a subset of vascular endothelial ... ...

    Abstract Embryonic definitive hematopoiesis generates hematopoietic stem and progenitor cells (HSPCs) that are essential for the establishment and maintenance of the adult blood system. This process requires the specification of a subset of vascular endothelial cells (ECs) to become hemogenic ECs and to have subsequent endothelial-to-hematopoietic transition (EHT), and the underlying mechanisms are largely undefined. We identified microRNA (miR)-223 as a negative regulator of murine hemogenic EC specification and EHT. Loss of miR-223 leads to increased formation of hemogenic ECs and HSPCs, which is associated with increased retinoic acid signaling, which we previously showed as promoting hemogenic EC specification. Additionally, loss of miR-223 leads to the generation of myeloid-biased hemogenic ECs and HSPCs, which results in an increased proportion of myeloid cells throughout embryonic and postnatal life. Our findings identify a negative regulator of hemogenic EC specification and highlight the importance of this process for the establishment of the adult blood system.
    MeSH term(s) Mice ; Animals ; Hemangioblasts ; Myelopoiesis/genetics ; Hematopoietic Stem Cells ; Hematopoiesis/genetics ; Cell Differentiation ; MicroRNAs/genetics
    Chemical Substances MicroRNAs ; MIRN223 microRNA, mouse
    Language English
    Publishing date 2023-06-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2023.05.007
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  5. Book: Cardiovascular regenerative biology

    Badylak, Stephen F. / Hirschi, Karen K. / Niklason, Laura E.

    5 tables

    (Cells, tissues, organs ; 195,1/2)

    2012  

    Author's details guest ed. Stephen F. Badylak ; Karen K. Hirschi ; Laura E. Niklason
    Series title Cells, tissues, organs ; 195,1/2
    Cells tissues organs
    Collection Cells tissues organs
    Language English
    Size 183 S. : Ill., graph. Darst.
    Publisher Karger
    Publishing place Basel u.a.
    Publishing country Switzerland
    Document type Book
    HBZ-ID HT017079071
    ISBN 978-3-8055-9872-9 ; 9783805598736 ; 3-8055-9872-6 ; 3805598734
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    Ub I Zs 150 -195- verfügbar in Königswinter Königswinter

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  6. Article: Single Cell Analysis in Vascular Biology.

    Chavkin, Nicholas W / Hirschi, Karen K

    Frontiers in cardiovascular medicine

    2020  Volume 7, Page(s) 42

    Abstract: The ability to quantify DNA, RNA, and protein variations at the single cell level has revolutionized our understanding of cellular heterogeneity within tissues. Via such analyses, individual cells within populations previously thought to be homogeneous ... ...

    Abstract The ability to quantify DNA, RNA, and protein variations at the single cell level has revolutionized our understanding of cellular heterogeneity within tissues. Via such analyses, individual cells within populations previously thought to be homogeneous can now be delineated into specific subpopulations expressing unique sets of genes, enabling specialized functions. In vascular biology, studies using single cell RNA sequencing have revealed extensive heterogeneity among endothelial and mural cells even within the same vessel, key intermediate cell types that arise during blood and lymphatic vessel development, and cell-type specific responses to disease. Thus, emerging new single cell analysis techniques are enabling vascular biologists to elucidate mechanisms of vascular development, homeostasis, and disease that were previously not possible. In this review, we will provide an overview of single cell analysis methods and highlight recent advances in vascular biology made possible through single cell RNA sequencing.
    Language English
    Publishing date 2020-03-31
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2781496-8
    ISSN 2297-055X
    ISSN 2297-055X
    DOI 10.3389/fcvm.2020.00042
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  7. Article ; Online: Regulation of Hemogenic Endothelial Cell Development and Function.

    Wu, Yinyu / Hirschi, Karen K

    Annual review of physiology

    2020  Volume 83, Page(s) 17–37

    Abstract: Embryonic definitive hematopoiesis generates hematopoietic stem and progenitor cells (HSPCs) essential for establishment and maintenance of the adult blood system. This process requires the specification of a subset of vascular endothelial cells to ... ...

    Abstract Embryonic definitive hematopoiesis generates hematopoietic stem and progenitor cells (HSPCs) essential for establishment and maintenance of the adult blood system. This process requires the specification of a subset of vascular endothelial cells to become blood-forming, or hemogenic, and the subsequent endothelial-to-hematopoietic transition to generate HSPCs therefrom. The mechanisms that regulate these processes are under intensive investigation, as their recapitulation in vitro from human pluripotent stem cells has the potential to generate autologous HSPCs for clinical applications. In this review, we provide an overview of hemogenic endothelial cell development and highlight the molecular events that govern hemogenic specification of vascular endothelial cells and the generation of multilineage HSPCs from hemogenic endothelium. We also discuss the impact of hemogenic endothelial cell development on adult hematopoiesis.
    MeSH term(s) Animals ; Cell Differentiation/physiology ; Endothelial Cells/physiology ; Endothelium, Vascular/physiology ; Hemangioblasts/physiology ; Hematopoiesis/physiology ; Hematopoietic Stem Cells/physiology ; Humans
    Language English
    Publishing date 2020-10-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 207933-1
    ISSN 1545-1585 ; 0066-4278
    ISSN (online) 1545-1585
    ISSN 0066-4278
    DOI 10.1146/annurev-physiol-021119-034352
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  8. Article ; Online: Vascular endothelial cell specification in health and disease.

    Marziano, Corina / Genet, Gael / Hirschi, Karen K

    Angiogenesis

    2021  Volume 24, Issue 2, Page(s) 213–236

    Abstract: There are two vascular networks in mammals that coordinately function as the main supply and drainage systems of the body. The blood vasculature carries oxygen, nutrients, circulating cells, and soluble factors to and from every tissue. The lymphatic ... ...

    Abstract There are two vascular networks in mammals that coordinately function as the main supply and drainage systems of the body. The blood vasculature carries oxygen, nutrients, circulating cells, and soluble factors to and from every tissue. The lymphatic vasculature maintains interstitial fluid homeostasis, transports hematopoietic cells for immune surveillance, and absorbs fat from the gastrointestinal tract. These vascular systems consist of highly organized networks of specialized vessels including arteries, veins, capillaries, and lymphatic vessels that exhibit different structures and cellular composition enabling distinct functions. All vessels are composed of an inner layer of endothelial cells that are in direct contact with the circulating fluid; therefore, they are the first responders to circulating factors. However, endothelial cells are not homogenous; rather, they are a heterogenous population of specialized cells perfectly designed for the physiological demands of the vessel they constitute. This review provides an overview of the current knowledge of the specification of arterial, venous, capillary, and lymphatic endothelial cell identities during vascular development. We also discuss how the dysregulation of these processes can lead to vascular malformations, and therapeutic approaches that have been developed for their treatment.
    MeSH term(s) Animals ; Blood Vessels/metabolism ; Blood Vessels/pathology ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Humans ; Lymphatic Vessels/metabolism ; Lymphatic Vessels/pathology ; Vascular Malformations/metabolism ; Vascular Malformations/pathology
    Language English
    Publishing date 2021-04-12
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1484717-6
    ISSN 1573-7209 ; 0969-6970
    ISSN (online) 1573-7209
    ISSN 0969-6970
    DOI 10.1007/s10456-021-09785-7
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  9. Article ; Online: Molecular regulation of arteriovenous endothelial cell specification.

    Fang, Jennifer / Hirschi, Karen

    F1000Research

    2019  Volume 8

    Abstract: The systemic circulation depends upon a highly organized, hierarchal blood vascular network that requires the successful specification of arterial and venous endothelial cells during development. This process is driven by a cascade of signaling events ( ... ...

    Abstract The systemic circulation depends upon a highly organized, hierarchal blood vascular network that requires the successful specification of arterial and venous endothelial cells during development. This process is driven by a cascade of signaling events (including Hedgehog, vascular endothelial growth factor (VEGF), Notch, connexin (Cx), transforming growth factor-beta (TGF- β), and COUP transcription factor 2 (COUP-TFII)) to influence endothelial cell cycle status and expression of arterial or venous genes and is further regulated by hemodynamic flow. Failure of endothelial cells to properly undergo arteriovenous specification may contribute to vascular malformation and dysfunction, such as in hereditary hemorrhagic telangiectasia (HHT) and capillary malformation-arteriovenous malformation (CM-AVM) where abnormal vessel structures, such as large shunts lacking clear arteriovenous identity and function, thereby compromising peripheral blood flow. This review provides an overview of recent findings in the field of arteriovenous specification and highlights key regulators of this process.
    MeSH term(s) COUP Transcription Factor II ; Cell Cycle ; Endothelial Cells/physiology ; Humans ; Signal Transduction ; Vascular Endothelial Growth Factor A ; Veins
    Chemical Substances COUP Transcription Factor II ; Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2019-07-29
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2699932-8
    ISSN 2046-1402 ; 2046-1402
    ISSN (online) 2046-1402
    ISSN 2046-1402
    DOI 10.12688/f1000research.16701.1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Endothelial Cell Development and Its Application to Regenerative Medicine.

    Qiu, Jingyao / Hirschi, Karen K

    Circulation research

    2019  Volume 125, Issue 4, Page(s) 489–501

    Abstract: The formation and remodeling of a functional circulatory system is critical for sustaining prenatal and postnatal life. During embryogenesis, newly differentiated endothelial cells require further specification to create the unique features of distinct ... ...

    Abstract The formation and remodeling of a functional circulatory system is critical for sustaining prenatal and postnatal life. During embryogenesis, newly differentiated endothelial cells require further specification to create the unique features of distinct vessel subtypes needed to support tissue morphogenesis. In this review, we explore signaling pathways and transcriptional regulators that modulate endothelial cell differentiation and specification, as well as applications of these processes to stem cell biology and regenerative medicine. We also summarize recent technical advances, including the growing utilization of single-cell sequencing to study vascular heterogeneity and development.
    MeSH term(s) Animals ; Endothelial Progenitor Cells/cytology ; Endothelial Progenitor Cells/metabolism ; Endothelium, Vascular/cytology ; Endothelium, Vascular/physiology ; Humans ; Neovascularization, Physiologic ; Regenerative Medicine/methods
    Language English
    Publishing date 2019-08-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.119.311405
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