Light-sheet fluorescence imaging charts the gastrula origin of vascular endothelial cells in early zebrafish embryos

Abstract It remains challenging to construct a complete cell lineage map of the origin of vascular endothelial cells in any vertebrate embryo. Here, we report the application of in toto light-sheet fluorescence imaging of embryos to trace the origin of vascular endothelial cells (ECs) at single-cell resolution in zebrafish. We first adapted a previously reported method to embryo mounting and light-sheet imaging, created an alignment, fusion, and extraction all-in-one software (AFEIO) for processing big data, and performed quantitative analysis of cell lineage relationships using commercially available Imaris software. Our data revealed that vascular ECs originated from broad regions of the gastrula along the dorsal–ventral and anterior–posterior axes, of which the dorsal–anterior cells contributed to cerebral ECs, the dorsal–lateral cells to anterior trunk ECs, and the ventral–lateral cells to posterior trunk and tail ECs. Therefore, this work, to our knowledge, charts the first comprehensive map of the gastrula origin of vascular ECs in zebrafish, and has potential applications for studying the origin of any embryonic organs in zebrafish and other model organisms.

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Light-Sheet Fluorescence Imaging Charts the Gastrula Origin of Vascular Endothelial Cells in Early Zebrafish Embryos

10.1101/2020.05.27.118661 ◽

2020 ◽

Author(s):

Meijun Pang ◽

Linlu Bai ◽

Weijian Zong ◽

Xu Wang ◽

Ye Bu ◽

...

Keyword(s):

Endothelial Cells ◽

Fluorescence Imaging ◽

Vascular Endothelial Cells ◽

Cell Lineage ◽

Light Sheet ◽

Model Organisms ◽

Vascular Endothelial ◽

Anterior Trunk ◽

Potential Applications ◽

Complete Cell

AbstractIt remains challenging to construct a complete cell lineage map of the origin of vascular endothelial cells in any vertebrate embryo. Here, we report the application of in toto light-sheet fluorescence imaging of embryos to tracing the origin of vascular endothelial cells (ECs) at single-cell resolution in zebrafish. We first adapted a previously-reported method to mount embryos and light-sheet imaging, created an alignment, fusion, and extraction all-in-one software (AFEIO) for processing big data, and performed quantitative analysis of cell lineage relationships using commercially-available Imaris software. Our data revealed that vascular ECs originated from broad regions of the gastrula along the dorsal-ventral and anterior-posterior axes, of which the dorsal-anterior cells contributed to cerebral ECs, the dorsal-lateral cells to anterior trunk ECs, and the ventral-lateral cells to posterior trunk and tail ECs. Therefore, this work, to our knowledge, charts the first comprehensive map of the gastrula origin of vascular ECs in zebrafish, and has potential applications for studying the origin of any embryonic organs in zebrafish and other model organisms.

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Vascular endothelial cell lineage-specific promoter in transgenic mice

Development ◽

10.1242/dev.121.4.1089 ◽

1995 ◽

Vol 121 (4) ◽

pp. 1089-1098 ◽

Cited By ~ 5

Author(s):

T.M. Schlaeger ◽

Y. Qin ◽

Y. Fujiwara ◽

J. Magram ◽

T.N. Sato

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Vascular Endothelial Cells ◽

Es Cells ◽

Vascular Endothelial Cell ◽

Cell Lineage ◽

Vascular Endothelial ◽

Lacz Reporter

Vascular endothelial cells play essential roles in the function and development of the cardiovascular system. However, due to the lack of lineage-specific markers suitable for molecular and biochemical analyses, very little is known about the molecular mechanisms that regulate endothelial cell differentiation. We report the first vascular endothelial cell lineage-specific (including angioblastic precursor cells) 1.2 kb promoter in transgenic mice. Moreover, deletion analysis of this promoter region in transgenic embryos revealed multiple elements that are required for the maximum endothelial cell lineage-specific expression. This is a powerful molecular tool that will enable us to identify factors and cellular signals essential for the establishment of vascular endothelial cell lineage. It will also allow us to deliver genes specifically into this cell type in vivo to test specifically molecules that have been implicated in cardiovascular development. Furthermore, we have established embryonic stem (ES) cells from the blastocysts of the transgenic mouse that carry the 1.2 kb promoter-LacZ reporter transgene. These ES cells were able to differentiate in vitro to form cystic embryoid bodies (CEB) that contain endothelial cells determined by PECAM immunohistochemistry. However, these in vitro differentiated endothelial cells did not express the LacZ reporter gene. This indicates the lack of factors and/or cellular interactions which are required to induce the expression of the reporter gene mediated by this 1.2 kb promoter in this in vitro differentiation system. Thus this system will allow us to screen for the putative inducers that exist in vivo but not in vitro. These putative inducers are presumably important for in vivo differentiation of vascular endothelial cells.

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Regional specification and complementation with non-neuroectodermal cells in human brain organoids

Journal of Molecular Medicine ◽

10.1007/s00109-021-02051-9 ◽

2021 ◽

Vol 99 (4) ◽

pp. 489-500 ◽

Cited By ~ 1

Author(s):

Yoshiaki Tanaka ◽

In-Hyun Park

Keyword(s):

Endothelial Cells ◽

Disease Modeling ◽

Vascular Endothelial Cells ◽

Brain Regions ◽

Cell Reprogramming ◽

Vascular Endothelial ◽

The Past ◽

Somatic Cell Reprogramming ◽

Potential Applications ◽

Neural Disorders

AbstractAlong with emergence of the organoids, their application in biomedical research has been currently one of the most fascinating themes. For the past few years, scientists have made significant contributions to deriving organoids representing the whole brain and specific brain regions. Coupled with somatic cell reprogramming and CRISPR/Cas9 editing, the organoid technologies were applied for disease modeling and drug screening. The methods to develop organoids further improved for rapid and efficient generation of cerebral organoids. Additionally, refining the methods to develop the regionally specified brain organoids enabled the investigation of development and interaction of the specific brain regions. Recent studies started resolving the issue in the lack of non-neuroectodermal cells in brain organoids, including vascular endothelial cells and microglia, which play fundamental roles in neurodevelopment and are involved in the pathophysiology of acute and chronic neural disorders. In this review, we highlight recent advances of neuronal organoid technologies, focusing on the region-specific brain organoids and complementation with endothelial cells and microglia, and discuss their potential applications to neuronal diseases.

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Vascular Notch Signaling in Stress Hematopoiesis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.606448 ◽

2021 ◽

Vol 8 ◽

Author(s):

Can Huang ◽

Dawei Yang ◽

George W. Ye ◽

Charles A. Powell ◽

Peipei Guo

Keyword(s):

Endothelial Cells ◽

Notch Signaling ◽

Cell Fate ◽

Stromal Cell ◽

Vascular Endothelial Cells ◽

Cell Lineage ◽

Transgenic Animals ◽

Cell Types ◽

Vascular Endothelial ◽

Hematopoietic Stem

Canonical Notch signaling is one of the most conserved signaling cascades. It regulates cell proliferation, cell differentiation, and cell fate maintenance in a variety of biological systems during development and cancer (Fortini, 2009; Kopan and Ilagan, 2009; Andersson et al., 2011; Ntziachristos et al., 2014). For the hematopoietic system, during embryonic development, Notch1 is essential for the emergence of hematopoietic stem cells (HSCs) at the aorta-gornado-mesonephro regions of the dorsal aorta. At adult stage, Notch receptors and Notch targets are expressed at different levels in diverse hematopoietic cell types and influence lineage choices. For example, Notch specifies T cell lineage over B cells. However, there has been a long-lasting debate on whether Notch signaling is required for the maintenance of adult HSCs, utilizing transgenic animals inactivating different components of the Notch signaling pathway in HSCs or niche cells. The aims of the current mini-review are to summarize the evidence that disapproves or supports such hypothesis and point at imperative questions waiting to be addressed; hence, some of the seemingly contradictory findings could be reconciled. We need to better delineate the Notch signaling events using biochemical assays to identify direct Notch targets within HSCs or niche cells in specific biological context. More importantly, we call for more elaborate studies that pertain to whether niche cell type (vascular endothelial cells or other stromal cell)-specific Notch ligands regulate the differentiation of T cells in solid tumors during the progression of T-lymphoblastic lymphoma (T-ALL) or chronic myelomonocytic leukemia (CMML). We believe that the investigation of vascular endothelial cells' or other stromal cell types' interaction with hematopoietic cells during homeostasis and stress can offer insights toward specific and effective Notch-related therapeutics.

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Investigation of the effect of tanshinone IIA on nitric oxide production in human vascular endothelial cells by fluorescence imaging

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy ◽

10.1016/j.saa.2007.01.029 ◽

2007 ◽

Vol 68 (5) ◽

pp. 1180-1186 ◽

Cited By ~ 25

Author(s):

Ke-Jing Huang ◽

Hong Wang ◽

Wan-Zhen Xie ◽

Hua-Shan Zhang

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Fluorescence Imaging ◽

Vascular Endothelial Cells ◽

Tanshinone Iia ◽

Nitric Oxide Production ◽

Vascular Endothelial ◽

Oxide Production

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M.629 Homocysteine inhibits lysyl oxidase (LOX) and downregulates LOX expression in vascular endothelial cells

Atherosclerosis ◽

10.1016/s0021-9150(04)90627-2 ◽

2004 ◽

Vol 5 (1) ◽

pp. 146

Author(s):

B RAPOSO

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Lysyl Oxidase ◽

Vascular Endothelial

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Anti-metalloproteinase-9 Activities of Selected Indonesian Zingiberaceae Rhizome Extracts in Lipopolysaccharide-induced Human Vascular Endothelial Cells In Vitro

Planta Medica ◽

10.1055/s-0031-1282610 ◽

2011 ◽

Vol 77 (12) ◽

Author(s):

Y Yanti ◽

N Steven ◽

A Wiharja ◽

S Fajarianto

Keyword(s):

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Metalloproteinase 9

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The Endothelial Cell and the Factor VIII Bypassing Activity of Prothrombin Complex Concentrate

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647034 ◽

1988 ◽

Vol 60 (02) ◽

pp. 226-229 ◽

Cited By ~ 2

Author(s):

Jerome M Teitel ◽

Hong-Yu Ni ◽

John J Freedman ◽

M Bernadette Garvey

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Factor Viii ◽

Prothrombin Complex Concentrate ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Monolayer Cultures ◽

Coagulant Activity ◽

Time Courses ◽

Privileged Site

SummarySome classical hemophiliacs have a paradoxical hemostatic response to prothrombin complex concentrate (PCC). We hypothesized that vascular endothelial cells (EC) may contribute to this “factor VIII bypassing activity”. When PCC were incubated with suspensions or monolayer cultures of EC, they acquired the ability to partially bypass the defect of factor VIII deficient plasma. This factor VIII bypassing activity distributed with EC and not with the supernatant PCC, and was not a general property of intravascular cells. The effect of PCC was even more dramatic on fixed EC monolayers, which became procoagulant after incubation with PCC. The time courses of association and dissociation of the PCC-derived factor VIII bypassing activity of fixed and viable EC monolayers were both rapid. We conclude that EC may provide a privileged site for sequestration of constituents of PCC which express coagulant activity and which bypass the abnormality of factor VIII deficient plasma.

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Alterations in Vascular Endothelial Cell-related Plasma Proteins In Thalassaemic Patients and their Correlation with Clinical Symptoms

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649879 ◽

1995 ◽

Vol 74 (04) ◽

pp. 1045-1049 ◽

Cited By ~ 38

Author(s):

P Butthep ◽

A Bunyaratvej ◽

Y Funahara ◽

H Kitaguchi ◽

S Fucharoen ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Immunosorbent Assay ◽

Plasma Proteins ◽

Clinical Symptoms ◽

Vascular Endothelial Cells ◽

Vascular Endothelial Cell ◽

Enzyme Linked Immunosorbent Assay ◽

Vascular Endothelial ◽

Leg Ulcers

SummaryAn increased level of plasma thrombomodulin (TM) in α- and β- thalassaemia was demonstrated using an enzyme-linked immunosorbent assay (ELISA). Nonsplenectomized patients with β-thalassaemia/ haemoglobin E (BE) had higher levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU) were found to have the highest increase in TM level. Appearance of larger platelets in all types of thalassaemic blood was observed indicating an increase in the number of younger platelets. These data indicate that injury of vascular endothelial cells is present in thalassaemic patients.

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