Published ahead of print on March 31, 2005, doi:10.1165/rcmb.2005-0024OC Am. J. Respir. Cell Mol. Biol., Volume 33, Number 1, July 2005, 32-40 A more recent version of this article appeared on July 1, 2005
Submitted on January 12, 2005 Embryonic Lung Side Population Cells are Hematopoietic and Vascular PrecursorsRoss Summer1*,1 Pulmonary Center, Boston University School of Medicine, Boston, MA, USA * To whom correspondence should be addressed. E-mail: rsummer{at}lung.bumc.bu.edu.
Side population cells (SP) are a select cell population identified by a capacity to efflux Hoechst dye that are highly enriched for stem/progenitor cell activity. In this paper, we found that SP cells comprised of CD45 (+) and CD45 (-) subtypes are present in the embryonic lung (E-SP) at levels varying with gestational age. Long-term in vivo competitive blood reconstitution studies demonstrated that hematopoeitic stem cell capacity resided within the CD45 (+) E-SP cell subset. Immuno-phenotyping of CD45(-) E-SP cells determined that this population consists of two subtypes; CD31(-) and CD31(+). Limited gene expression profiling indicated that CD45(-)/CD31(-) E-SP cells have features of smooth muscle precursors, and give rise to smooth muscle in culture. On the other hand, CD45(-)/CD31(+) E-SP cells express genes characteristic of endothelium, but by themselves do not grow or differentiate in culture. Co-culture of CD45(-)/CD31(+) and CD45(-)/CD31(-) E-SP cells, however, resulted in the formation of complex tubular networks that express markers of endothelium. Together, these findings illustrate that embryonic lung SP cells are heterogeneous, composed of hematopoeitic and non-hematopoeitic progenitors, and may play a key role in the formation of the lung vasculature.
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