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Hemogenic endothelium

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https://www.readbyqxmd.com/read/28416284/distinct-roles-for-matrix-metalloproteinases-2-and-9-in-embryonic-hematopoietic-stem-cell-emergence-migration-and-niche-colonization
#1
Lindsay N Theodore, Elliott J Hagedorn, Mauricio Cortes, Kelsey Natsuhara, Sarah Y Liu, Julie R Perlin, Song Yang, Madeleine L Daily, Leonard I Zon, Trista E North
Hematopoietic stem/progenitor cells (HSPCs) are formed during ontogeny from hemogenic endothelium in the ventral wall of the dorsal aorta (VDA). Critically, the cellular mechanism(s) allowing HSPC egress and migration to secondary niches are incompletely understood. Matrix metalloproteinases (MMPs) are inflammation-responsive proteins that regulate extracellular matrix (ECM) remodeling, cellular interactions, and signaling. Here, inhibition of vascular-associated Mmp2 function caused accumulation of fibronectin-rich ECM, retention of runx1/cmyb(+) HSPCs in the VDA, and delayed caudal hematopoietic tissue (CHT) colonization; these defects were absent in fibronectin mutants, indicating that Mmp2 facilitates endothelial-to-hematopoietic transition via ECM remodeling...
April 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28338096/identification-of-cardiac-hemo-vascular-precursors-and-their-requirement-of-sphingosine-1-phosphate-receptor-1-for-heart-development
#2
Yan Hu, Brian C Belyea, Minghong Li, Joachim R Göthert, R Ariel Gomez, Maria Luisa S Sequeira-Lopez
The cardiac endothelium plays a crucial role in the development of a functional heart. However, the precise identification of the endocardial precursors and the mechanisms they require for their role in heart morphogenesis are not well understood. Using in vivo and in vitro cell fate tracing concomitant with specific cell ablation and embryonic heart transplantation studies, we identified a unique set of precursors which possess hemogenic functions and express the stem cell leukemia (SCL) gene driven by its 5' enhancer...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302184/cytokine-free-directed-differentiation-of-human-pluripotent-stem-cells-efficiently-produces-hemogenic-endothelium-with-lymphoid-potential
#3
Yekaterina Galat, Svetlana Dambaeva, Irina Elcheva, Aaruni Khanolkar, Kenneth Beaman, Philip M Iannaccone, Vasiliy Galat
BACKGROUND: The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification...
March 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28299650/the-role-of-runx1-in-embryonic-blood-cell-formation
#4
Amanda D Yzaguirre, Marella F T R de Bruijn, Nancy A Speck
The de novo generation of hematopoietic stem and progenitor cells (HSPC) occurs solely during embryogenesis from a population of epithelial cells called hemogenic endothelium (HE). During midgestation HE cells in multiple intra- and extraembryonic vascular beds leave the vessel wall as they transition into HSPCs in a process termed the endothelial to hematopoietic transition (EHT). Runx1 expression in HE cells orchestrates the transcriptional switch necessary for the transdifferentiation of endothelial cells into functional HSPCs...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28271994/nkx2-5-marks-angioblasts-that-contribute-to-hemogenic-endothelium-of-the-endocardium-and-dorsal-aorta
#5
Lyad Zamir, Reena Singh, Elisha Nathan, Ralph Patrick, Oren Yifa, Yfat Yahalom-Ronen, Alaa A Arraf, Thomas M Schultheiss, Shengbao Suo, Jing-Dong Jackie Han, Guangdun Peng, Naihe Jing, Yuliang Wang, Nathan Palpant, Patrick Pl Tam, Richard P Harvey, Eldad Tzahor
Novel regenerative therapies may stem from deeper understanding of the mechanisms governing cardiovascular lineage diversification. Using enhancer mapping and live imaging in avian embryos, and genetic lineage tracing in mice, we investigated the spatio-temporal dynamics of cardiovascular progenitor populations. We show that expression of the cardiac transcription factor Nkx2.5 marks a mesodermal population outside of the cardiac crescent in the extraembryonic and lateral plate mesoderm, with characteristics of hemogenic angioblasts...
March 8, 2017: ELife
https://www.readbyqxmd.com/read/28090699/modelling-irf8-deficient-human-hematopoiesis-and-dendritic-cell-development-with-engineered-ips-cells
#6
Stephanie Sontag, Malrun Förster, Jie Qin, Paul Wanek, Saskia Mitzka, Herdit M Schüler, Steffen Koschmieder, Stefan Rose-John, Kristin Seré, Martin Zenke
Human induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers, including hematopoietic stem cells and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining factor for myeloid cells, including dendritic cells (DC). Autosomal recessive or dominant IRF8 mutations occurring in patients cause severe monocytic and DC immunodeficiency. To study IRF8 in human hematopoiesis we generated human IRF8-/- iPS cells and IRF8-/- embryonic stem (ES) cells using RNA guided CRISPR/Cas9n genome editing...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28087636/r-spondin-1-is-required-for-specification-of-hematopoietic-stem-cells-through-wnt16-and-vegfa-signaling-pathways
#7
Jamie R Genthe, Wilson K Clements
Hematopoietic stem cells (HSCs) are the therapeutic component of bone marrow transplants, but finding immune-compatible donors limits treatment availability and efficacy. Recapitulation of endogenous specification during development is a promising approach to directing HSC specification in vitro, but current protocols are not capable of generating authentic HSCs with high efficiency. Across phyla, HSCs arise from hemogenic endothelium in the ventral floor of the dorsal aorta concurrent with arteriovenous specification and intersegmental vessel (ISV) sprouting, processes regulated by Notch and Wnt...
February 15, 2017: Development
https://www.readbyqxmd.com/read/28043822/hemangioblast-hemogenic-endothelium-and-primitive-versus-definitive-hematopoiesis
#8
REVIEW
Georges Lacaud, Valerie Kouskoff
The types of progenitors generated during the successive stages of embryonic blood development are now fairly well characterized. The terminology used to describe these waves, however, can still be confusing. What is truly primitive? What is uniquely definitive? These questions become even more challenging to answer when blood progenitors are derived in vitro upon the differentiation of embryonic stem cells or induced pluripotent stem cells. Similarly, the cellular origin of these blood progenitors can be controversial...
December 30, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27880904/lyve1-marks-the-divergence-of-yolk-sac-definitive-hemogenic-endothelium-from-the-primitive-erythroid-lineage
#9
Lydia K Lee, Yasamine Ghorbanian, Wenyuan Wang, Yanling Wang, Yeon Joo Kim, Irving L Weissman, Matthew A Inlay, Hanna K A Mikkola
The contribution of the different waves and sites of developmental hematopoiesis to fetal and adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS) endothelium and definitive hematopoietic stem and progenitor cells (HSPCs). Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta and placenta, were labeled by Lyve1-Cre. Most YS HSPCs and erythro-myeloid progenitors were Lyve1-Cre lineage traced, but primitive erythroid cells were not, suggesting that they represent distinct lineages...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27861498/somite-derived-retinoic-acid-regulates-zebrafish-hematopoietic-stem-cell-formation
#10
Laura M Pillay, Kacey J Mackowetzky, Sonya A Widen, Andrew Jan Waskiewicz
Hematopoietic stem cells (HSCs) are multipotent progenitors that generate all vertebrate adult blood lineages. Recent analyses have highlighted the importance of somite-derived signaling factors in regulating HSC specification and emergence from dorsal aorta hemogenic endothelium. However, these factors remain largely uncharacterized. We provide evidence that the vitamin A derivative retinoic acid (RA) functions as an essential regulator of zebrafish HSC formation. Temporal analyses indicate that RA is required for HSC gene expression prior to dorsal aorta formation, at a time when the predominant RA synthesis enzyme, aldh1a2, is strongly expressed within the paraxial mesoderm and somites...
2016: PloS One
https://www.readbyqxmd.com/read/27802172/interplay-between-sox7-and-runx1-regulates-hemogenic-endothelial-fate-in-the-yolk-sac
#11
Andrew J Lilly, Guilherme Costa, Anne Largeot, Muhammad Z H Fadlullah, Michael Lie-A-Ling, Georges Lacaud, Valerie Kouskoff
Endothelial to hematopoietic transition (EHT) is a dynamic process involving the shutting down of endothelial gene expression and switching on of hematopoietic gene transcription. Although the factors regulating EHT in hemogenic endothelium (HE) of the dorsal aorta have been relatively well studied, the molecular regulation of yolk sac HE remains poorly understood. Here, we show that SOX7 inhibits the expression of RUNX1 target genes in HE, while having no effect on RUNX1 expression itself. We establish that SOX7 directly interacts with RUNX1 and inhibits its transcriptional activity...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27760216/nitric-oxide-donor-molsidomine-positively-modulates-myogenic-differentiation-of-embryonic-endothelial-progenitors
#12
Mario Tirone, Valentina Conti, Fabio Manenti, Pier Andrea Nicolosi, Cristina D'Orlando, Emanuele Azzoni, Silvia Brunelli
Embryonic VE-Cadherin-expressing progenitors (eVE-Cad+), including hemogenic endothelium, have been shown to generate hematopoietic stem cells and a variety of other progenitors, including mesoangioblasts, or MABs. MABs are vessel-associated progenitors with multilineage mesodermal differentiation potential that can physiologically contribute to skeletal muscle development and regeneration, and have been used in an ex vivo cell therapy setting for the treatment of muscular dystrophy. There is currently a therapeutic need for molecules that could improve the efficacy of cell therapy protocols; one such good candidate is nitric oxide...
2016: PloS One
https://www.readbyqxmd.com/read/27638855/evi1-regulates-notch-activation-to-induce-zebrafish-hematopoietic-stem-cell-emergence
#13
Martina Konantz, Elisa Alghisi, Joëlle S Müller, Anna Lenard, Virginie Esain, Kelli J Carroll, Lothar Kanz, Trista E North, Claudia Lengerke
During development, hematopoietic stem cells (HSCs) emerge from aortic endothelial cells (ECs) through an intermediate stage called hemogenic endothelium by a process known as endothelial-to-hematopoietic transition (EHT). While Notch signaling, including its upstream regulator Vegf, is known to regulate this process, the precise molecular control and temporal specificity of Notch activity remain unclear. Here, we identify the zebrafish transcriptional regulator evi1 as critically required for Notch-mediated EHT In vivo live imaging studies indicate that evi1 suppression impairs EC progression to hematopoietic fate and therefore HSC emergence...
November 2, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27597316/origin-of-the-hematopoietic-system-in-the-human-embryo
#14
Emmanuelle Julien, Reine El Omar, Manuela Tavian
The continuous generation of blood cells throughout life relies on the existence of hematopoietic stem cells (HSC) generated during embryogenesis. Given the importance of HSC transplantation in cell-based therapeutic approaches, considerable efforts have been made toward understanding the developmental origins of embryonic HSC. Adult-type HSC are first generated in the aorta-gonad-mesonephros (AGM) region between days 27 and 40 of human embryonic development, but an elusive blood-forming potential is present earlier in the underlying splanchnopleura...
September 6, 2016: FEBS Letters
https://www.readbyqxmd.com/read/27554085/identification-of-novel-regulators-of-developmental-hematopoiesis-using-endoglin-regulatory-elements-as-molecular-probes
#15
Rabab Nasrallah, Eva M Fast, Parham Solaimani, Kathy Knezevic, Alexia Eliades, Rahima Patel, Roshana Thambyrajah, Ashwin Unnikrishnan, Julie Thoms, Dominik Beck, Chris S Vink, Aileen Smith, Jason Wong, Mairi Shepherd, David Kent, Rahul Roychoudhuri, Fabian Paul, Julia Klippert, Annette Hammes, Thomas Willnow, Bertie Göttgens, Elaine Dzierzak, Leonard I Zon, George Lacaud, Valerie Kouskoff, John E Pimanda
Enhancers are the primary determinants of cell identity, and specific promoter/enhancer combinations of Endoglin (ENG) have been shown to target blood and endothelium in the embryo. Here, we generated a series of embryonic stem cell lines, each targeted with reporter constructs driven by specific promoter/enhancer combinations of ENG, to evaluate their discriminative potential and value as molecular probes of the corresponding transcriptome. The Eng promoter (P) in combination with the -8/+7/+9-kb enhancers, targeted cells in FLK1 mesoderm that were enriched for blast colony forming potential, whereas the P/-8-kb enhancer targeted TIE2+/c-KIT+/CD41- endothelial cells that were enriched for hematopoietic potential...
October 13, 2016: Blood
https://www.readbyqxmd.com/read/27499523/transforming-growth-factor-%C3%AE-drives-hemogenic-endothelium-programming-and-the-transition-to-hematopoietic-stem-cells
#16
Rui Monteiro, Philip Pinheiro, Nicola Joseph, Tessa Peterkin, Jana Koth, Emmanouela Repapi, Florian Bonkhofer, Arif Kirmizitas, Roger Patient
Hematopoietic stem cells (HSCs) are self-renewing multipotent stem cells that generate mature blood lineages throughout life. They, together with hematopoietic progenitor cells (collectively known as HSPCs), emerge from hemogenic endothelium in the floor of the embryonic dorsal aorta by an endothelial-to-hematopoietic transition (EHT). Here we demonstrate that transforming growth factor β (TGFβ) is required for HSPC specification and that it regulates the expression of the Notch ligand Jagged1a in endothelial cells prior to EHT, in a striking parallel with the epithelial-to-mesenchymal transition (EMT)...
August 22, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27399214/new-insights-into-the-regulation-by-runx1-and-gfi1-s-proteins-of-the-endothelial-to-hematopoietic-transition-generating-primordial-hematopoietic-cells
#17
Roshana Thambyrajah, Rahima Patel, Milena Mazan, Michael Lie-A-Ling, Andrew Lilly, Alexia Eliades, Sara Menegatti, Eva Garcia-Alegria, Magdalena Florkowska, Kiran Batta, Valerie Kouskoff, Georges Lacaud
The first hematopoietic cells are generated very early in ontogeny to support the growth of the embryo and to provide the foundation to the adult hematopoietic system. There is a considerable therapeutic interest in understanding how these first blood cells are generated in order to try to reproduce this process in vitro. This would allow generating blood products, or hematopoietic cell populations from embryonic stem (ES) cells, induced pluripotent stem cells or through directed reprogramming. Recent studies have clearly established that the first hematopoietic cells originate from a hemogenic endothelium (HE) through an endothelial to hematopoietic transition (EHT)...
August 17, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27391301/generating-human-hematopoietic-stem-cells-in-vitro-exploring-endothelial-to-hematopoietic-transition-as-a-portal-for-stemness-acquisition
#18
REVIEW
Igor I Slukvin
Advances in cellular reprogramming technologies have created alternative platforms for the production of blood cells, either through inducing pluripotency in somatic cells or by way of direct conversion of nonhematopoietic cells into blood cells. However, de novo generation of hematopoietic stem cells (HSCs) with robust and sustained multilineage engraftment potential remains a significant challenge. Hemogenic endothelium (HE) has been recognized as a unique transitional stage of blood development from mesoderm at which HSCs arise in certain embryonic locations...
November 2016: FEBS Letters
https://www.readbyqxmd.com/read/27389484/insights-into-blood-cell-formation-from-hemogenic-endothelium-in-lesser-known-anatomic-sites
#19
Amanda D Yzaguirre, Nancy A Speck
BACKGROUND: Hematopoietic stem and progenitor cells (HSPCs) are generated de novo in the embryo in a process termed the endothelial to hematopoietic transition (EHT). EHT is most extensively studied in the yolk sac and dorsal aorta. Recently new sites of hematopoiesis have been described, including the heart, somites, head, and venous plexus of the yolk sac. RESULTS: We examined sites of HSPC formation in well-studied and in less well-known sites by mapping the expression of the key EHT factor Runx1 along with several other markers by means of confocal microscopy...
October 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/27341393/isolation-of-murine-embryonic-hemogenic-endothelial-cells
#20
Jennifer S Fang, Emily C Gritz, Kathrina L Marcelo, Karen K Hirschi
The specification of hemogenic endothelial cells from embryonic vascular endothelium occurs during brief developmental periods within distinct tissues, and is necessary for the emergence of definitive HSPC from the murine extra embryonic yolk sac, placenta, umbilical vessels, and the embryonic aorta-gonad-mesonephros (AGM) region. The transient nature and small size of this cell population renders its reproducible isolation for careful quantification and experimental applications technically difficult. We have established a fluorescence-activated cell sorting (FACS)-based protocol for simultaneous isolation of hemogenic endothelial cells and HSPC during their peak generation times in the yolk sac and AGM...
June 17, 2016: Journal of Visualized Experiments: JoVE
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