|
|
|
|||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Development, Vol 124, Issue 10 2039-2048, Copyright © 1997 by Company of Biologists
JOURNAL ARTICLES |
N Kabrun, HJ Buhring, K Choi, A Ullrich, W Risau and G Keller
National Jewish Medical and Research Center, Denver, CO 80206, USA.
We have investigated the expression pattern of the Flk-1 receptor tyrosine kinase in mouse embryonic and fetal hematopoietic tissues as well as on hematopoietic precursor cells derived from these tissues. RNA analysis indicated that flk-1 was expressed in the yolk sac at day 10 of gestation, in the whole embryo at day 10 and 12 of gestation, in the liver throughout fetal life and in embryoid bodies (EBs) generated from ES cells differentiated in culture. Flk-1 message was also detected in erythroid and macrophage colonies generated from precursors of yolk sac, fetal liver, adult marrow and EB origin. Using an antibody directed against the extracellular portion of the molecule we have found that up to 50% of cells from EBs differentiated for 4 days express Flk-1. Following the development of this early Flk-1+ population the number of receptor-positive cells declines progressively to represent less than 5% of the EBs by day 12 of differentiation. Kinetic analysis revealed that the establishment of the EB Flk-1+ population precedes the development of cells which express CD34, Ly6A (Sca-1) and AA4.1. Cell sorting experiments demonstrated that all day-4 EB-derived hematopoietic precursors are Flk-1+ whereas greater than 95% of those found within the day-12 EBs are Flk-1-, suggesting that the precursor population which expresses this receptor represents an early but transient wave of hematopoietic development. Analysis of yolk sac and whole embryos at day 8.5 of gestation revealed a small but distinct Flk-1+ population that contained hematopoietic precursors. Day-12.5 fetal liver contained few Flk-1+ cells that showed little hematopoietic potential. Together these findings indicate that Flk-1 is expressed on an early population of hematopoietic precursors that may represent the onset of embryonic hematopoiesis.
This article has been cited by other articles:
![]() |
X. Li, D. Edholm, F. Lanner, G. Breier, F. Farnebo, A. Dimberg, and L. Claesson-Welsh Lentiviral Rescue of Vascular Endothelial Growth Factor Receptor-2 Expression in Flk1 / Embryonic Stem Cells Shows Early Priming of Endothelial Precursors Stem Cells, December 1, 2007; 25(12): 2987 - 2995. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. C. R. Perlingeiro Endoglin is required for hemangioblast and early hematopoietic development Development, August 15, 2007; 134(16): 3041 - 3048. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Haremaki, S. T. Fraser, Y.-M. Kuo, M. H. Baron, and D. C. Weinstein Vertebrate Ctr1 coordinates morphogenesis and progenitor cell fate and regulates embryonic stem cell differentiation PNAS, July 17, 2007; 104(29): 12029 - 12034. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Takenaga, M. Fukumoto, and Y. Hori Regulated Nodal signaling promotes differentiation of the definitive endoderm and mesoderm from ES cells J. Cell Sci., June 15, 2007; 120(12): 2078 - 2090. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. K. Bone and M. J. Welham Phosphoinositide 3-kinase signalling regulates early development and developmental haemopoiesis J. Cell Sci., May 15, 2007; 120(10): 1752 - 1762. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Kennedy, S. L. D'Souza, M. Lynch-Kattman, S. Schwantz, and G. Keller Development of the hemangioblast defines the onset of hematopoiesis in human ES cell differentiation cultures Blood, April 1, 2007; 109(7): 2679 - 2687. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Kriz, N. Agren, C. K. Lindholm, S. Lenell, J. Saldeen, J. Mares, and M. Welsh The SHB Adapter Protein Is Required for Normal Maturation of Mesoderm during in Vitro Differentiation of Embryonic Stem Cells J. Biol. Chem., November 10, 2006; 281(45): 34484 - 34491. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Rolny, I. Nilsson, P. Magnusson, A. Armulik, L. Jakobsson, P. Wentzel, P. Lindblom, J. Norlin, C. Betsholtz, R. Heuchel, et al. Platelet-derived growth factor receptor-beta promotes early endothelial cell differentiation Blood, September 15, 2006; 108(6): 1877 - 1886. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Camara-Clayette, F. Le Pesteur, W. Vainchenker, and F. Sainteny Quantitative Oct4 Overproduction in Mouse Embryonic Stem Cells Results in Prolonged Mesoderm Commitment During Hematopoietic Differentiation In Vitro Stem Cells, August 1, 2006; 24(8): 1937 - 1945. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Furuta, H. Ema, S.-i. Takayanagi, T. Ogaeri, D. Okamura, Y. Matsui, and H. Nakauchi Discordant developmental waves of angioblasts and hemangioblasts in the early gastrulating mouse embryo. Development, July 1, 2006; 133(14): 2771 - 2779. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Wang, P. C. Charles, Y. Wu, R. Ren, X. Pi, M. Moser, M. Barshishat-Kupper, J. S. Rubin, C. Perou, V. Bautch, et al. Gene Expression Profile Signatures Indicate a Role for Wnt Signaling in Endothelial Commitment From Embryonic Stem Cells Circ. Res., May 26, 2006; 98(10): 1331 - 1339. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Priddle, D. R. E. Jones, P. W. Burridge, and R. Patient Hematopoiesis from Human Embryonic Stem Cells: Overcoming the Immune Barrier in Stem Cell Therapies Stem Cells, April 1, 2006; 24(4): 815 - 824. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Matsumoto, A. Kubo, H. Liu, K. Akita, F. Laub, F. Ramirez, G. Keller, and S. L. Friedman Developmental regulation of yolk sac hematopoiesis by Kruppel-like factor 6 Blood, February 15, 2006; 107(4): 1357 - 1365. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. L Bautch Flk1 expression: promiscuity revealed Blood, January 1, 2006; 107(1): 3 - 4. [Full Text] [PDF] |
||||
![]() |
H. Hirai, I. M Samokhvalov, T. Fujimoto, S. Nishikawa, J. Imanishi, and S.-I. Nishikawa Involvement of Runx1 in the down-regulation of fetal liver kinase-1 expression during transition of endothelial cells to hematopoietic cells Blood, September 15, 2005; 106(6): 1948 - 1955. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. D. Zheng, K. Hidaka, and T. Morisaki Stable and Uniform Gene Suppression by Site-Specific Integration of siRNA Expression Cassette in Murine Embryonic Stem Cells Stem Cells, September 1, 2005; 23(8): 1028 - 1034. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. T. Zambidis, B. Peault, T. S. Park, F. Bunz, and C. I. Civin Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac development Blood, August 1, 2005; 106(3): 860 - 870. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Kubo, V. Chen, M. Kennedy, E. Zahradka, G. Q. Daley, and G. Keller The homeobox gene HEX regulates proliferation and differentiation of hemangioblasts and endothelial cells during ES cell differentiation Blood, June 15, 2005; 105(12): 4590 - 4597. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Keller Embryonic stem cell differentiation: emergence of a new era in biology and medicine Genes & Dev., May 15, 2005; 19(10): 1129 - 1155. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. L. D'Souza, A. G. Elefanty, and G. Keller SCL/Tal-1 is essential for hematopoietic commitment of the hemangioblast but not for its development Blood, May 15, 2005; 105(10): 3862 - 3870. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Irie, T. Tatsumi, M. Takamiya, K. Zen, T. Takahashi, A. Azuma, K. Tateishi, T. Nomura, H. Hayashi, N. Nakajima, et al. Carbon Dioxide-Rich Water Bathing Enhances Collateral Blood Flow in Ischemic Hindlimb via Mobilization of Endothelial Progenitor Cells and Activation of NO-cGMP System Circulation, March 29, 2005; 111(12): 1523 - 1529. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Iida, T. Heike, M. Yoshimoto, S. Baba, H. Doi, and T. Nakahata Identification of cardiac stem cells with FLK1, CD31, and VE-cadherin expression during embryonic stem cell differentiation FASEB J, March 1, 2005; 19(3): 371 - 378. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. S. Ng, L. Azzola, K. Sourris, L. Robb, E. G. Stanley, and A. G. Elefanty The primitive streak gene Mixl1 is required for efficient haematopoiesis and BMP4-induced ventral mesoderm patterning in differentiating ES cells Development, March 1, 2005; 132(5): 873 - 884. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Eguchi, M. Eguchi-Ishimae, A. Green, T. Enver, and M. Greaves Directing oncogenic fusion genes into stem cells via an SCL enhancer PNAS, January 25, 2005; 102(4): 1133 - 1138. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. M. Dikov, J. E. Ohm, N. Ray, E. E. Tchekneva, J. Burlison, D. Moghanaki, S. Nadaf, and D. P. Carbone Differential Roles of Vascular Endothelial Growth Factor Receptors 1 and 2 in Dendritic Cell Differentiation J. Immunol., January 1, 2005; 174(1): 215 - 222. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Tsuneto, A. Tominaga, H. Yamazaki, M. Yoshino, S. H. Orkin, and S.-I. Hayashi Enforced Expression of PU.1 Rescues Osteoclastogenesis from Embryonic Stem Cells Lacking Tal-1 Stem Cells, January 1, 2005; 23(1): 134 - 143. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. K. Hadland, S. S. Huppert, J. Kanungo, Y. Xue, R. Jiang, T. Gridley, R. A. Conlon, A. M. Cheng, R. Kopan, and G. D. Longmore A requirement for Notch1 distinguishes 2 phases of definitive hematopoiesis during development Blood, November 15, 2004; 104(10): 3097 - 3105. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Menthena, N. Deb, M. Oertel, P. N. Grozdanov, J. Sandhu, S. Shah, C. Guha, D. A. Shafritz, and M. D. Dabeva Bone Marrow Progenitors Are Not the Source of Expanding Oval Cells in Injured Liver Stem Cells, November 1, 2004; 22(6): 1049 - 1061. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. R. Gothert, S. E. Gustin, J. A. M. van Eekelen, U. Schmidt, M. A. Hall, S. M. Jane, A. R. Green, B. Gottgens, D. J. Izon, and C. G. Begley Genetically tagging endothelial cells in vivo: bone marrow-derived cells do not contribute to tumor endothelium Blood, September 15, 2004; 104(6): 1769 - 1777. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Ferrara Vascular Endothelial Growth Factor: Basic Science and Clinical Progress Endocr. Rev., August 1, 2004; 25(4): 581 - 611. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Cerdan, A. Rouleau, and M. Bhatia VEGF-A165 augments erythropoietic development from human embryonic stem cells Blood, April 1, 2004; 103(7): 2504 - 2512. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Magnusson, C. Rolny, L. Jakobsson, C. Wikner, Y. Wu, D. J. Hicklin, and L. Claesson-Welsh Deregulation of Flk-1/vascular endothelial growth factor receptor-2 in fibroblast growth factor receptor-1-deficient vascular stem cell development J. Cell Sci., March 15, 2004; 117(8): 1513 - 1523. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Martin, R. Lahlil, A. Damert, L. Miquerol, A. Nagy, G. Keller, and T. Hoang SCL interacts with VEGF to suppress apoptosis at the onset of hematopoiesis Development, February 1, 2004; 131(3): 693 - 702. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. M. Nadin, M. A. Goodell, and K. K. Hirschi Phenotype and hematopoietic potential of side population cells throughout embryonic development Blood, October 1, 2003; 102(7): 2436 - 2443. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. D. Johnson, J. A. Grass, C. Park, H. Im, K. Choi, and E. H. Bresnick Highly Restricted Localization of RNA Polymerase II within a Locus Control Region of a Tissue-Specific Chromatin Domain Mol. Cell. Biol., September 15, 2003; 23(18): 6484 - 6493. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Ferkowicz, M. Starr, X. Xie, W. Li, S. A. Johnson, W. C. Shelley, P. R. Morrison, and M. C. Yoder CD41 expression defines the onset of primitive and definitive hematopoiesis in the murine embryo Development, September 15, 2003; 130(18): 4393 - 4403. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. J. Fehling, G. Lacaud, A. Kubo, M. Kennedy, S. Robertson, G. Keller, and V. Kouskoff Tracking mesoderm induction and its specification to the hemangioblast during embryonic stem cell differentiation Development, September 1, 2003; 130(17): 4217 - 4227. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. F. de Pooter, S. K. Cho, J. R. Carlyle, and J. C. Zuniga-Pflucker In vitro generation of T lymphocytes from embryonic stem cell-derived prehematopoietic progenitors Blood, September 1, 2003; 102(5): 1649 - 1653. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Moser, O. Binder, Y. Wu, J. Aitsebaomo, R. Ren, C. Bode, V. L. Bautch, F. L. Conlon, and C. Patterson BMPER, a Novel Endothelial Cell Precursor-Derived Protein, Antagonizes Bone Morphogenetic Protein Signaling and Endothelial Cell Differentiation Mol. Cell. Biol., August 15, 2003; 23(16): 5664 - 5679. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Nakayama, D. Duryea, R. Manoukian, G. Chow, and C.-y. E. Han Macroscopic cartilage formation with embryonic stem-cell-derived mesodermal progenitor cells J. Cell Sci., May 15, 2003; 116(10): 2015 - 2028. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Im, C. Park, Q. Feng, K. D. Johnson, C. M. Kiekhaefer, K. Choi, Y. Zhang, and E. H. Bresnick Dynamic Regulation of Histone H3 Methylated at Lysine 79 within a Tissue-specific Chromatin Domain J. Biol. Chem., May 9, 2003; 278(20): 18346 - 18352. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. C.R. Perlingeiro, M. Kyba, S. Bodie, and G. Q. Daley A Role for Thrombopoietin in Hemangioblast Development Stem Cells, May 1, 2003; 21(3): 272 - 280. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Kubo and K. Alitalo The bloody fate of endothelial stem cells Genes & Dev., February 1, 2003; 17(3): 322 - 329. [Full Text] [PDF] |
||||
![]() |
H. Hirai, M. Ogawa, N. Suzuki, M. Yamamoto, G. Breier, O. Mazda, J. Imanishi, and S.-I. Nishikawa Hemogenic and nonhemogenic endothelium can be distinguished by the activity of fetal liver kinase (Flk)-1 promoter/enhancer during mouse embryogenesis Blood, February 1, 2003; 101(3): 886 - 893. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Lacaud, L. Gore, M. Kennedy, V. Kouskoff, P. Kingsley, C. Hogan, L. Carlsson, N. Speck, J. Palis, and G. Keller Runx1 is essential for hematopoietic commitment at the hemangioblast stage of development in vitro Blood, June 28, 2002; 100(2): 458 - 466. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Fruttiger Development of the Mouse Retinal Vasculature: Angiogenesis Versus Vasculogenesis Invest. Ophthalmol. Vis. Sci., February 1, 2002; 43(2): 522 - 527. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. S. Chung, W. J. Zhang, E. Arentson, P. D. Kingsley, J. Palis, and K. Choi Lineage analysis of the hemangioblast as defined by FLK1 and SCL expression Development, January 12, 2002; 129(23): 5511 - 5520. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. K. Cho, A. Bourdeau, M. Letarte, and J. C. Zuniga-Pflucker Expression and function of CD105 during the onset of hematopoiesis from Flk1+ precursors Blood, December 15, 2001; 98(13): 3635 - 3642. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. L. Ramirez-Bergeron and M. C. Simon Hypoxia-Inducible Factor and the Development of Stem Cells of the Cardiovascular System Stem Cells, July 1, 2001; 19(4): 279 - 286. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Böldicke, M. Tesar, C. Griesel, M. Rohde, H.-J. Gröne, J. Waltenberger, O. Kollet, T. Lapidot, A. Yayon, and H. Weich Anti-VEGFR-2 scFvs for Cell Isolation. Single-Chain Antibodies Recognizing the Human Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2/flk-1) on the Surface of Primary Endothelial Cells and Preselected CD34+ Cells from Cord Blood Stem Cells, January 1, 2001; 19(1): 24 - 36. [Abstract] [Full Text] |
||||
![]() |
D.-Q. Guo, L.-W. Wu, J. D. Dunbar, O. N. Ozes, L. D. Mayo, K. M. Kessler, J. A. Gustin, M. R. Baerwald, E. A. Jaffe, R. S. Warren, et al. Tumor Necrosis Factor Employs a Protein-tyrosine Phosphatase to Inhibit Activation of KDR and Vascular Endothelial Cell Growth Factor-induced Endothelial Cell Proliferation J. Biol. Chem., April 6, 2000; 275(15): 11216 - 11221. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Nakayama, J. Lee, and L. Chiu Vascular endothelial growth factor synergistically enhances bone morphogenetic protein-4-dependent lymphohematopoietic cell generation from embryonic stem cells in vitro Blood, April 1, 2000; 95(7): 2275 - 2283. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. J. Drake and P. A. Fleming Vasculogenesis in the day 6.5 to 9.5 mouse embryo Blood, March 1, 2000; 95(5): 1671 - 1679. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Robertson, M Kennedy, J. Shannon, and G Keller A transitional stage in the commitment of mesoderm to hematopoiesis requiring the transcription factor SCL/tal-1 Development, January 6, 2000; 127(11): 2447 - 2459. [Abstract] [PDF] |
||||
![]() |
P Faloon, E Arentson, A Kazarov, C. Deng, C Porcher, S Orkin, and K Choi Basic fibroblast growth factor positively regulates hematopoietic development Development, January 5, 2000; 127(9): 1931 - 1941. [Abstract] [PDF] |
||||
![]() |
S. A. Stacker, A. Vitali, C. Caesar, T. Domagala, L. C. Groenen, E. Nice, M. G. Achen, and A. F. Wilks A Mutant Form of Vascular Endothelial Growth Factor (VEGF) That Lacks VEGF Receptor-2 Activation Retains the Ability to Induce Vascular Permeability J. Biol. Chem., December 3, 1999; 274(49): 34884 - 34892. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. L. Ziegler, M. Valtieri, G. A. Porada, R. D. Maria, R. Müller, B. Masella, M. Gabbianelli, I. Casella, E. Pelosi, T. Bock, et al. KDR Receptor: A Key Marker Defining Hematopoietic Stem Cells Science, September 3, 1999; 285(5433): 1553 - 1558. [Abstract] [Full Text] |
||||
![]() |
M. Hidaka, W. L. Stanford, and A. Bernstein Conditional requirement for the Flk-1 receptor in the in vitro generation of early hematopoietic cells PNAS, June 22, 1999; 96(13): 7370 - 7375. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Kappel, V. Ronicke, A. Damert, I. Flamme, W. Risau, and G. Breier Identification of Vascular Endothelial Growth Factor (VEGF) Receptor-2 (Flk-1) Promoter/Enhancer Sequences Sufficient for Angioblast and Endothelial Cell-Specific Transcription in Transgenic Mice Blood, June 15, 1999; 93(12): 4284 - 4292. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Ribatti, M. Presta, A. Vacca, R. Ria, R. Giuliani, P. Dell'Era, B. Nico, L. Roncali, and F. Dammacco Human Erythropoietin Induces a Pro-Angiogenic Phenotype in Cultured Endothelial Cells and Stimulates Neovascularization In Vivo Blood, April 15, 1999; 93(8): 2627 - 2636. [Abstract] [Full Text] [PDF] |
||||