Abstract
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].
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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 Sca-1 was found to be more robustly expressed in postnatal pups than in embryos (Uchida K, unpublished observation), suggesting that a subset of Sca-1-expressing cells may be related to the formation of the capillary network during later development.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).
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.
References
Summer R, Kotton DN, Liang S, et al. Embryonic lung side population cells are hematopoietic and vascular precursors. Am J Respir Cell Mol Biol. 2005;33:32–40.
McQualter JL, Brouard N, Williams B, et al. Endogenous fibroblastic progenitor cells in the adult mouse lung are highly enriched in the Sca-1 positive cell fraction. Stem Cells. 2009;27:623–33.
Kotton DN, Summer RS, Sun X, et al. Stem cell antigen-1 expression in the pulmonary vascular endothelium. Am J Physiol Lung Cell Mol Physiol. 2003;284:L990–6.
Acknowledgment
This work was supported by JSPS KAKENHI Grant Number JP16K10074 to J.M.
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Maeda, J., Uchida, K., Kodo, K., Yamagishi, H. (2020). Roles of Stem Cell Antigen-1 in the Pulmonary Endothelium. In: Nakanishi, T., Baldwin, H., Fineman, J., Yamagishi, H. (eds) Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension. Springer, Singapore. https://doi.org/10.1007/978-981-15-1185-1_10
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DOI: https://doi.org/10.1007/978-981-15-1185-1_10
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