scholarly journals Gata2 is required for HSC generation and survival

2013 ◽  
Vol 210 (13) ◽  
pp. 2843-2850 ◽  
Author(s):  
Emma de Pater ◽  
Polynikis Kaimakis ◽  
Chris S. Vink ◽  
Tomomasa Yokomizo ◽  
Tomoko Yamada-Inagawa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Developmental Stages ◽  
Vascular Endothelial ◽  
Vascular Integrity ◽  
Hematopoietic Stem ◽  
Vascular Endothelial Cadherin ◽  
Umbilical Arteries ◽  
Specific Deletion

Knowledge of the key transcription factors that drive hematopoietic stem cell (HSC) generation is of particular importance for current hematopoietic regenerative approaches and reprogramming strategies. Whereas GATA2 has long been implicated as a hematopoietic transcription factor and its dysregulated expression is associated with human immunodeficiency syndromes and vascular integrity, it is as yet unknown how GATA2 functions in the generation of HSCs. HSCs are generated from endothelial cells of the major embryonic vasculature (aorta, vitelline, and umbilical arteries) and are found in intra-aortic hematopoietic clusters. In this study, we find that GATA2 function is essential for the generation of HSCs during the stage of endothelial-to-hematopoietic cell transition. Specific deletion of Gata2 in Vec (Vascular Endothelial Cadherin)-expressing endothelial cells results in a deficiency of long-term repopulating HSCs and intra-aortic cluster cells. By specific deletion of Gata2 in Vav-expressing hematopoietic cells (after HSC generation), we further show that GATA2 is essential for HSC survival. This is in contrast to the known activity of the RUNX1 transcription factor, which functions only in the generation of HSCs, and highlights the unique requirement for GATA2 function in HSCs throughout all developmental stages.

scholarly journals Hierarchical organization and early hematopoietic specification of the developing HSC lineage in the AGM region

2011 ◽  
Vol 208 (6) ◽  
pp. 1305-1315 ◽  
Author(s):  
Stanislav Rybtsov ◽  
Malgorzata Sobiesiak ◽  
Samir Taoudi ◽  
Céline Souilhol ◽  
Jordi Senserrich ◽  
...  
Keyword(s):  
Hierarchical Organization ◽  
Major Type ◽  
Type I ◽  
Vascular Endothelial ◽  
Type Ii ◽  
Hematopoietic Stem ◽  
Vascular Endothelial Cadherin ◽  
Genetic Tagging

The aorta-gonad-mesonephros region plays an important role in hematopoietic stem cell (HSC) development during mouse embryogenesis. The vascular endothelial cadherin+ CD45+ (VE-cad+CD45+) population contains the major type of immature pre-HSCs capable of developing into long-term repopulating definitive HSCs. In this study, we developed a new coaggregation culture system, which supports maturation of a novel population of CD45-negative (VE-cad+CD45−CD41+) pre-HSCs into definitive HSCs. The appearance of these pre-HSCs precedes development of the VE-cad+CD45+ pre-HSCs (termed here type I and type II pre-HSCs, respectively), thus establishing a hierarchical directionality in the developing HSC lineage. By labeling the luminal surface of the dorsal aorta, we show that both type I and type II pre-HSCs are distributed broadly within the endothelial and subendothelial aortic layers, in contrast to mature definitive HSCs which localize to the aortic endothelial layer. In agreement with expression of CD41 in pre-HSCs, in vivo CD41-Cre–mediated genetic tagging occurs in embryonic pre-HSCs and persists in all lymphomyeloid lineages of the adult animal.

Stealthy Nanoparticles Protecting Endothelium Barrier from Leakiness by Resisting the Absorption of VE-cadherin

Nanoscale ◽  
2021 ◽  
Author(s):  
Yuan Huang ◽  
Suxiao Wang ◽  
Jin-Zhi Zhang ◽  
Hang-Xing Wang ◽  
Qichao Zou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Interstitial Space ◽  
Cell Interactions ◽  
Vascular Endothelial ◽  
Vascular Endothelial Cadherin ◽  
Cell Cell

Nanomaterial induced endothelial cells leakiness (NanoEL) is caused because nanomaterials enter the interstitial space of endothelial cells and disrupt the endothelial cell-cell interactions by interacting with vascular endothelial cadherin (VE-cad)....

scholarly journals Emerging Role of AP-1 Transcription Factor JunB in Angiogenesis and Vascular Development

2021 ◽  
Vol 22 (6) ◽  
pp. 2804
Author(s):  
Yasuo Yoshitomi ◽  
Takayuki Ikeda ◽  
Hidehito Saito-Takatsuji ◽  
Hideto Yonekura
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Blood Vessel ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Blood Vessel Formation ◽  
Vessel Formation

Blood vessels are essential for the formation and maintenance of almost all functional tissues. They play fundamental roles in the supply of oxygen and nutrition, as well as development and morphogenesis. Vascular endothelial cells are the main factor in blood vessel formation. Recently, research findings showed heterogeneity in vascular endothelial cells in different tissue/organs. Endothelial cells alter their gene expressions depending on their cell fate or angiogenic states of vascular development in normal and pathological processes. Studies on gene regulation in endothelial cells demonstrated that the activator protein 1 (AP-1) transcription factors are implicated in angiogenesis and vascular development. In particular, it has been revealed that JunB (a member of the AP-1 transcription factor family) is transiently induced in endothelial cells at the angiogenic frontier and controls them on tip cells specification during vascular development. Moreover, JunB plays a role in tissue-specific vascular maturation processes during neurovascular interaction in mouse embryonic skin and retina vasculatures. Thus, JunB appears to be a new angiogenic factor that induces endothelial cell migration and sprouting particularly in neurovascular interaction during vascular development. In this review, we discuss the recently identified role of JunB in endothelial cells and blood vessel formation.

Live imaging of Runx1 expression in the dorsal aorta tracks the emergence of blood progenitors from endothelial cells

Blood ◽  
2010 ◽  
Vol 116 (6) ◽  
pp. 909-914 ◽  
Author(s):  
Enid Yi Ni Lam ◽  
Christopher J. Hall ◽  
Philip S. Crosier ◽  
Kathryn E. Crosier ◽  
Maria Vega Flores
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Fluorescent Protein ◽  
Living Organism ◽  
Time Lapse ◽  
Dorsal Aorta ◽  
Transgenic Zebrafish ◽  
Hematopoietic Stem ◽  
Green Fluorescent

Abstract Blood cells of an adult vertebrate are continuously generated by hematopoietic stem cells (HSCs) that originate during embryonic life within the aorta-gonad-mesonephros region. There is now compelling in vivo evidence that HSCs are generated from aortic endothelial cells and that this process is critically regulated by the transcription factor Runx1. By time-lapse microscopy of Runx1-enhanced green fluorescent protein transgenic zebrafish embryos, we were able to capture a subset of cells within the ventral endothelium of the dorsal aorta, as they acquire hemogenic properties and directly emerge as presumptive HSCs. These nascent hematopoietic cells assume a rounded morphology, transiently occupy the subaortic space, and eventually enter the circulation via the caudal vein. Cell tracing showed that these cells subsequently populated the sites of definitive hematopoiesis (thymus and kidney), consistent with an HSC identity. HSC numbers depended on activity of the transcription factor Runx1, on blood flow, and on proper development of the dorsal aorta (features in common with mammals). This study captures the earliest events of the transition of endothelial cells to a hemogenic endothelium and demonstrates that embryonic hematopoietic progenitors directly differentiate from endothelial cells within a living organism.

scholarly journals Endothelial Cells Promote Expansion of Long-Term Engrafting Marrow Hematopoietic Stem and Progenitor Cells in Primates

2016 ◽  
Vol 6 (3) ◽  
pp. 864-876 ◽  
Author(s):  
Jennifer L. Gori ◽  
Jason M. Butler ◽  
Balvir Kunar ◽  
Michael G. Poulos ◽  
Michael Ginsberg ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

scholarly journals Transient Exposure of Endothelial Cells to Doxorubicin Leads to Long-Lasting Vascular Endothelial Growth Factor Receptor 2 Downregulation

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 210
Author(s):  
Silvia Graziani ◽  
Luca Scorrano ◽  
Giovanna Pontarin
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Drug Withdrawal ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
P53 Expression ◽  
Endothelial Growth Factor

Doxorubicin (Dox) is an effective antineoplastic drug with serious cardiotoxic side effects that persist after drug withdrawal and can lead to heart failure. Dysregulation of vascular endothelium has been linked to the development of Dox-induced cardiotoxicity, but it is unclear whether and how transient exposure to Dox leads to long-term downregulation of Endothelial Vascular Endothelial Growth Factor Receptor type2 (VEGFR2), essential for endothelial cells function. Using an in vitro model devised to study the long-lasting effects of brief endothelial cells exposure to Dox, we show that Dox leads to sustained protein synthesis inhibition and VEGFR2 downregulation. Transient Dox treatment led to the development of long-term senescence associated with a reduction in VEGFR2 levels that persisted days after drug withdrawal. By analyzing VEGFR2 turnover, we ruled out that its downregulation was depended on Dox-induced autophagy. Conversely, Dox induced p53 expression, reduced mTOR-dependent translation, and inhibited global protein synthesis. Our data contribute to a mechanistic basis to the permanent damage caused to endothelial cells by short-term Dox treatment.

scholarly journals Lepasnya Sel Endotel Dan Vascular Endothelial Cadherin (Ve-Cadherin) Pada Huvecs Dengan Glukosa Tinggi Dan Fluid Shear Stress

2020 ◽  
Vol 8 (2) ◽  
pp. 92
Author(s):  
Yoyon Arif ◽  
Erna Sulistiowati
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Vascular Endothelial ◽  
Fluid Shear ◽  
Vascular Endothelial Cadherin

Sel endotel melapisi lumen pembuluh darah sehingga menyebabkan paparan langsung aliran darah dan timbul gaya hemodinamik shear stress. Vascular Endothelial (VE) Cadherin merupakan salah satu struktur penghubung antar sel yang berperan mencegah terlepasnya sel endotel dari membran dasar. Paparan glukosa tinggi menyebabkan stress oksidatif sehingga sel endotel mengalami apoptosis dan nekrosis dan terlepas. Penelitian ini bertujuan mempelajari efek paparan glukosa tinggi dan fluid shear stress terhadap morfologi, struktur VE-Cadherin dan densitas sel endotel pada kultur sel endotel HUVECs (Human Vein Endothelial Cells Culture).Metode Penelitian eksperimental laboratorium dengan  metode HUVECs yang dipapar d-glukosa 22 mM selama 7 hari. Shear stress dibangkitkan dengan alat cone and plate 10 dyne/cm2 selama 5, 8, 12 dan 15 menit. Pulasan VE-Cadherin dengan imunohistokimia. Data dianalisis dengan metode statistik. Signifikan pada p<0,05.Hasil Shear stress selama 15 menit menyebabkan perubahan bentuk sel endotel  menjadi lebih panjang dan inti sel lebih pipih. Paparan glukosa tinggi dan fluid shear stress menyebabkan penurunan skor VE-Cadherin dan densitas sel endotel secara signifikan Penurunan skor VE-Cadherin berpengaruh langsung terhadap penurunan densitas sel endotel.Kesimpulan. Paparan glukosa tinggi dan fluid shear stress menyebabkan kerusakan struktur VE-Cadherin sehingga terjadi peningkatan apoptosis dan nekrosis sel endotel.

Cbfa2 is required for the formation of intra-aortic hematopoietic clusters

Development ◽  
1999 ◽  
Vol 126 (11) ◽  
pp. 2563-2575 ◽  
Author(s):  
T. North ◽  
T.L. Gu ◽  
T. Stacy ◽  
Q. Wang ◽  
L. Howard ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Hematopoietic Cells ◽  
Hematopoietic Progenitor Cells ◽  
Genital Ridge ◽  
Hematopoietic Progenitor ◽  
Dorsal Aspect ◽  
Umbilical Arteries ◽  
Primitive Erythropoiesis ◽  
Binding Subunit

Cbfa2 (AML1) encodes the DNA-binding subunit of a transcription factor in the small family of core-binding factors (CBFs). Cbfa2 is required for the differentiation of all definitive hematopoietic cells, but not for primitive erythropoiesis. Here we show that Cbfa2 is expressed in definitive hematopoietic progenitor cells, and in endothelial cells in sites from which these hematopoietic cells are thought to emerge. Endothelial cells expressing Cbfa2 are in the yolk sac, the vitelline and umbilical arteries, and in the ventral aspect of the dorsal aorta in the aorta/genital ridge/mesonephros (AGM) region. Endothelial cells lining the dorsal aspect of the aorta, and elsewhere in the embryo, do not express Cbfa2. Cbfa2 appears to be required for maintenance of Cbfa2 expression in the endothelium, and for the formation of intra-aortic hematopoietic clusters from the endothelium.

scholarly journals Soluble vascular endothelial-cadherin in CSF after subarachnoid hemorrhage

Neurology ◽  
2020 ◽  
Vol 94 (12) ◽  
pp. e1281-e1293
Author(s):  
Hajime Takase ◽  
Sherry Hsiang-Yi Chou ◽  
Gen Hamanaka ◽  
Ryo Ohtomo ◽  
Mohammad R. Islam ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Functional Outcome ◽  
External Ventricular Drain ◽  
Clinical Severity ◽  
Vascular Endothelial ◽  
Long Term Outcomes ◽  
Anterior Circulation ◽  
Vascular Endothelial Cadherin ◽  
Tnf Α

ObjectiveTo determine if CSF and plasma levels of soluble vascular endothelial (sVE)-cadherin are associated with functional outcome after subarachnoid hemorrhage (SAH) and to investigate sVE-cadherin effects on microglia.MethodsSerial CSF and plasma were collected from prospectively enrolled patients with nontraumatic SAH from a ruptured aneurysm in the anterior circulation and who required an external ventricular drain for clinical indications. Patients with normal-pressure hydrocephalus without SAH served as controls. For prospective assessment of long-term outcomes at 3 and 6 months after SAH, modified Rankin Scale scores (mRS) were obtained and dichotomized into good (mRS ≤ 2) vs poor (mRS > 2) outcome groups. For SAH severity, Hunt and Hess grade was assessed. Association of CSF sVE-cadherin levels with long-term outcomes, HH grade, and CSF tumor necrosis factor (TNF)-α levels were evaluated. sVE-cadherin effects on microglia were also studied.ResultssVE-cadherin levels in CSF, but not in plasma, were higher in patients with SAH and were associated with higher clinical severity and higher CSF TNF-α levels. Patients with SAH with higher CSF sVE-cadherin levels over time were more likely to develop worse functional outcome at 3 months after SAH. Incubation of cultured microglia with sVE-cadherin resulted in increased inducible nitric oxide synthase, interleukin-1β, reactive oxygen species, cell soma size, and metabolic activity, consistent with microglia activation. Microinjection of sVE-cadherin fragments into mouse brain results in an increased number of microglia surrounding the injection site, compared to injection of denatured vascular endothelial–cadherin fragments.ConclusionsThese results support the existence of a novel pathway by which sVE-cadherin, released from injured endothelium after SAH, can shift microglia into a more proinflammatory phenotype and contribute to neuroinflammation and poor outcome in SAH.

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