© The Author(s) 2020
T. Nakanishi et al. (eds.)Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertensionhttps://doi.org/10.1007/978-981-15-1185-1_10

10. Roles of Stem Cell Antigen-1 in the Pulmonary Endothelium

Jun Maeda1, Keiko Uchida1, Kazuki Kodo1 and Hiroyuki Yamagishi2  
(1)
Department of Pediatrics, Keio University School of Medicine, Shinjuku, Tokyo, Japan
(2)
Division of Pediatric Cardiology, Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan
 
 
Hiroyuki Yamagishi
Email: hyamag@keio.jp
Keywords
Resident progenitor cellPulmonary vesselsSca-1Angiogenesis

There is growing evidence that resident progenitor cell populations exist in murine lung tissues and differentiate into a mesenchymal cell lineage [1, 2]. Stem cell antigen-1 (Sca-1) is a cell surface glycoprotein, initially found in murine bone marrow–derived stem cell subtypes, such as hematopoietic stem cells. Some studies showed Sca-1 expression in the pulmonary vascular endothelium of adult murine lungs [3], while a subset of Sca-1-expressing cells formed vascular-like structures under specific conditions [1].

We previously performed DNA microarray analysis using murine lung cells positive for vascular endothelial marker, CD31, selected by fluorescence-activated cell sorting (FACS) at embryonic and postnatal stages. Sca-1 was found to be more robustly expressed in postnatal pups than in embryos (Uchida K, unpublished observation), suggesting that a subset of Sca-1-expressing cells may be related to the formation of the capillary network during later development.

First, we performed immunohistochemistry using eight-week-old murine lung sections where Sca-1 immunostaining was found in the vascular wall of pulmonary vessels and alveolar capillaries. Some of these Sca-1-positive cells showed overlapping expression with vascular endothelial marker, vWF. Cell populations were then isolated from whole-lung cells by FACS, using antibodies for Sca-1 and CD31, following the depletion of CD45-positive cells. We investigated the tube formation ability of these sorted cells cultured in endothelial growth media and found that Sca-1 (–) CD31 (+) cells were more robust in tube formation than Sca-1 (+) CD31 (+) cells (Fig. 10.1).
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Fig. 10.1.

The tube formation assay. The tube formation (arrows) reflecting angiogenesis is more robustly observed in Sca-1 (–) CD31 (+) cells than in Sca-1 (+) CD31 (+) cells. Scale bars, 100 μm

These results suggest that though Sca-1 (+) CD31 (+) cells form vascular tube structures, they have lower tube formation activity than Sca-1 (–) CD31 (+) cells. Sca-1 may possibly repress angiogenesis activity in the endothelial cells and potentially make progenitor cell populations stay resident in adult murine lungs. Further analysis would delineate the physiological function of Sca-1 in developing lungs through embryonic to adult stages.

Acknowledgment

This work was supported by JSPS KAKENHI Grant Number JP16K10074 to J.M.

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