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Circ Res. 2012 Mar 30;110(7):922-6. doi: 10.1161/CIRCRESAHA.112.266510. Epub 2012 Mar 6.

Islet1 derivatives in the heart are of both neural crest and second heart field origin.

Author information

  • 1Department of Cell and Developmental Biology, Cardiovascular Institute and Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.

Erratum in

  • Circ Res. 2012 May 25;110(11):e90.

Abstract

RATIONALE:

Islet1 (Isl1) has been proposed as a marker of cardiac progenitor cells derived from the second heart field and is utilized to identify and purify cardiac progenitors from murine and human specimens for ex vivo expansion. The use of Isl1 as a specific second heart field marker is dependent on its exclusion from other cardiac lineages such as neural crest.

OBJECTIVE:

Determine whether Isl1 is expressed by cardiac neural crest.

METHODS AND RESULTS:

We used an intersectional fate-mapping system using the RC::FrePe allele, which reports dual Flpe and Cre recombination. Combining Isl1(Cre/+), a SHF driver, and Wnt1::Flpe, a neural crest driver, with Rc::FrePe reveals that some Isl1 derivatives in the cardiac outflow tract derive from Wnt1-expressing neural crest progenitors. In contrast, no overlap was observed between Wnt1-derived neural crest and an alternative second heart field driver, Mef2c-AHF-Cre.

CONCLUSIONS:

Isl1 is not restricted to second heart field progenitors in the developing heart but also labels cardiac neural crest. The intersection of Isl1 and Wnt1 lineages within the heart provides a caveat to using Isl1 as an exclusive second heart field cardiac progenitor marker and suggests that some Isl1-expressing progenitor cells derived from embryos, embryonic stem cultures, or induced pluripotent stem cultures may be of neural crest lineage.

PMID:
22394517
[PubMed - indexed for MEDLINE]
PMCID:
PMC3355870
Free PMC Article
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