Embryonic lung side population cells are hematopoietic and vascular precursors.
Side population (SP) cells are a select cell population identified by a capacity to efflux Hoechst dye that are highly enriched for stem/progenitor cell activity. In this study, 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. Immunophenotyping 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 nonhematopoeitic progenitors, and may play a key role in the formation of the lung vasculature.
Summer
Ross
R
The Pulmonary Center, Boston University School of Medicine, MA 02118, USA. rsummer@lung.bumc.bu.edu
Kotton
Darrell N
DN
Liang
Simon
S
Fitzsimmons
Kathleen
K
Sun
Xi
X
Fine
Alan
A
D000818:Animals; D001808:Blood Vessels / Q000166:cytology; D016026:Bone Marrow Transplantation; D039481:CD11b Antigen / Q000096:biosynthesis; D002454:Cell Differentiation; D002469:Cell Separation; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006413:Hematopoietic System; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008168:Lung / Q000166:cytology* / Q000196:embryology*; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009130:Muscle, Smooth / Q000166:cytology; D009132:Muscles / Q000166:cytology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors
D039481:CD11b Antigen; D005353:Fibronectins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens