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  Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling

Lin, M. I., Emily N., P., Boatmann, S., Hagedorn, E. J., Trompouki, E., Satishchandran, S., et al. (2015). Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling. eLIFE, 4, e05544. doi:doi: 10.7554/eLife.05544.

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Lin , Michelle I1, Author
Emily N., Price1, Author
Boatmann, Sonja1, Author
Hagedorn, Elliott J.1, Author
Trompouki, Eirini2, Author              
Satishchandran, Sruthi1, Author
Carspecken, Charles W.1, Author
Uong, Audrey1, Author
DiBiase, Anthony1, Author
Yang, Song1, Author
Canver, Matthew C.1, Author
Dahlberg, Ann3, Author
Lu , Zhigang4, 5, Author
Zhang, Cheng Cheng5, 6, Author
Orkin, Stuart H.1, 7, Author
Bernstein, Iriwin D.3, Author
Aster, Jon C.8, Author
White, Richard M9, 10, 11, Author
Zon, Leonard I1, Author
Affiliations:
1Stem Cell Program and Divion of Hematology/Oncology, Howard Hughes Medical Institute, Boston's Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, USA, ou_persistent22              
2Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              
3Pediatric Oncology, Clinical Division, Fred Hutchinson Cancer Research Center, Seattle, USA, ou_persistent22              
4Department of Physiology, University of Texas Southwestern Medical Center, Dallas, USA, ou_persistent22              
5Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, USA, ou_persistent22              
6Department of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, Dallas, USA, ou_persistent22              
7Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, USA, ou_persistent22              
8Department of Pathology, Brigham and Women's Hospital, Boston, USA, ou_persistent22              
9Department of Cancer Biology, Memorial Sloan Kettering Cancer Center, New York, USA, ou_persistent22              
10Department of Genetics, Memorial Sloan Kettering Cancer Center, New York, USA, ou_persistent22              
11Deparment of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA, ou_persistent22              

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 Abstract: Angiopoietin-like proteins (angptls) are capable of ex vivo expansion of mouse and human hematopoietic stem and progenitor cells (HSPCs). Despite this intriguing ability, their mechanism is unknown. In this study, we show that angptl2 overexpression is sufficient to expand definitive HSPCs in zebrafish embryos. Angptl1/2 are required for definitive hematopoiesis and vascular specification of the hemogenic endothelium. The loss-of-function phenotype is reminiscent of the notch mutant mindbomb (mib), and a strong genetic interaction occurs between angptls and notch. Overexpressing angptl2 rescues mib while overexpressing notch rescues angptl1/2 morphants. Gene expression studies in ANGPTL2-stimulated CD34+ cells showed a strong MYC activation signature and myc overexpression in angptl1/2 morphants or mib restored HSPCs formation. ANGPTL2 can increase NOTCH activation in cultured cells and ANGPTL receptor interacted with NOTCH to regulate NOTCH cleavage. Together our data provide insight to the angptl-mediated notch activation through receptor interaction and subsequent activation of myc targets.

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Language(s): eng - English
 Dates: 2015-02-25
 Publication Status: Published in print
 Pages: 25
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: doi: 10.7554/eLife.05544
 Degree: -

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Title: eLIFE
Source Genre: Journal
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Pages: 25 Volume / Issue: 4 Sequence Number: - Start / End Page: e05544 Identifier: -