β1-integrin is a cell-autonomous factor mediating the Numb pathway for cardiac progenitor maintenance

Brian C. Gibbs, Lincoln Shenje, Peter Andersen, Matthew Miyamoto, Chulan Kwon

Research output: Contribution to journalArticlepeer-review

Abstract

Proper control of multipotent/stem cell number and fate is essential for ensuing organ formation during development. β1-integrin, a subfamily of cell surface receptors, has a conserved role in maintenance of multipotent/stem cells, including renal progenitor cells, follicle stem cells, epidermal stem cells and neural stem cells. However, it remains unclear whether β1-integrin has a role in cardiac progenitor cell (CPC) development. Here we show that a mesodermal deletion of β1-integrin decreases Isl1+ cell number in the second pharyngeal arch (PA2), where CPCs undergo renewal and expansion. Mesp1 lineage-specific mosaicism revealed that β1-integrin-deleted Isl1+ cells do not proliferate in the PA2. Consistently, β1-integrin-deleted Isl1+ CPCs failed to expand in vitro, independent of PA2 cells. β1-integrin co-localized and physically associated with Numb, a crucial regulator of CPC renewal and expansion. Importantly, Numb/Numbl-deleted CPCs showed dramatic reduction in β1-integrin levels. These findings suggest that β1-integrin is a key mediator of the Numb pathway in CPC maintenance.

Original languageEnglish (US)
Pages (from-to)256-260
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume500
Issue number2
DOIs
StatePublished - Jun 2 2018

Keywords

  • Cardiac development
  • Cardiac progenitor expansion
  • ES/iPS cells
  • Numb/Numbl
  • Second heart field
  • β1-integrin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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