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

Michelle I. Lin, Emily N. Price, Sonja Boatman, Elliott J. Hagedorn, Eirini Trompouki, Sruthi Satishchandran, Charles W. Carspecken, Audrey Uong, Anthony DiBiase, Song Yang, Matthew C. Canver, Ann Dahlberg, Zhigang Lu, Chengcheng Zhang, Stuart H. Orkin, Irwin D. Bernstein, Jon C. Aster, Richard M. White, Leonard I. Zon

Research output: Contribution to journalArticle

14 Citations (Scopus)

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. Here, 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.

Original languageEnglish (US)
JournaleLife
Volume2015
Issue number4
DOIs
StatePublished - Feb 25 2015

Fingerprint

Angiopoietins
Notch Receptors
Hematopoietic Stem Cells
Chemical activation
Proteins
Hemangioblasts
Gene expression
Cells
Hematopoiesis
Zebrafish
Specifications
Blood Vessels
Cultured Cells
Embryonic Structures
Phenotype
Gene Expression

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Lin, M. I., Price, E. N., Boatman, S., Hagedorn, E. J., Trompouki, E., Satishchandran, S., ... Zon, L. I. (2015). Angiopoietin-like proteins stimulate HSPC development through interaction with Notch receptor signaling. eLife, 2015(4). https://doi.org/10.7554/eLife.05544

Angiopoietin-like proteins stimulate HSPC development through interaction with Notch receptor signaling. / Lin, Michelle I.; Price, Emily N.; Boatman, Sonja; Hagedorn, Elliott J.; Trompouki, Eirini; Satishchandran, Sruthi; Carspecken, Charles W.; Uong, Audrey; DiBiase, Anthony; Yang, Song; Canver, Matthew C.; Dahlberg, Ann; Lu, Zhigang; Zhang, Chengcheng; Orkin, Stuart H.; Bernstein, Irwin D.; Aster, Jon C.; White, Richard M.; Zon, Leonard I.

In: eLife, Vol. 2015, No. 4, 25.02.2015.

Research output: Contribution to journalArticle

Lin, MI, Price, EN, Boatman, S, Hagedorn, EJ, Trompouki, E, Satishchandran, S, Carspecken, CW, Uong, A, DiBiase, A, Yang, S, Canver, MC, Dahlberg, A, Lu, Z, Zhang, C, Orkin, SH, Bernstein, ID, Aster, JC, White, RM & Zon, LI 2015, 'Angiopoietin-like proteins stimulate HSPC development through interaction with Notch receptor signaling', eLife, vol. 2015, no. 4. https://doi.org/10.7554/eLife.05544
Lin MI, Price EN, Boatman S, Hagedorn EJ, Trompouki E, Satishchandran S et al. Angiopoietin-like proteins stimulate HSPC development through interaction with Notch receptor signaling. eLife. 2015 Feb 25;2015(4). https://doi.org/10.7554/eLife.05544
Lin, Michelle I. ; Price, Emily N. ; Boatman, Sonja ; Hagedorn, Elliott J. ; Trompouki, Eirini ; Satishchandran, Sruthi ; Carspecken, Charles W. ; Uong, Audrey ; DiBiase, Anthony ; Yang, Song ; Canver, Matthew C. ; Dahlberg, Ann ; Lu, Zhigang ; Zhang, Chengcheng ; Orkin, Stuart H. ; Bernstein, Irwin D. ; Aster, Jon C. ; White, Richard M. ; Zon, Leonard I. / Angiopoietin-like proteins stimulate HSPC development through interaction with Notch receptor signaling. In: eLife. 2015 ; Vol. 2015, No. 4.
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