Advertisement

Science China Life Sciences

, Volume 62, Issue 8, pp 1028–1037 | Cite as

Single-cell RNA sequencing profiling of the effects of aging on alveolar stem cells

  • Tingting Lv
  • Kewu Jiang
  • Jiawen Wang
  • Nan Tang
  • Huaping DaiEmail author
  • Chen WangEmail author
Research Paper

Abstract

The aging of alveolar stem cells has been linked to many chronic lung diseases, including pulmonary fibrosis. However, the effects of aging on alveolar stem cells during homeostasis and post-injury alveolar repair have not been well characterized. Here we conducted a single-cell RNA sequencing (scRNA-seq) analysis of alveolar stem cells of 3-month-old and 12-month-old mice to characterize the aging effect on alveolar stem cells. Our results have shown that the transcriptomes of alveolar stem cells of 3-month-old and 12-month-old mice are not significantly different under the steady condition. However, after a bleomycin-induced lung injury, the alveolar stem cells of 12-month-old mice show enhanced inflammatory responses and decreased lipid metabolism. Our study suggests a close relationship among aging, lipid metabolism, inflammatory responses and chronic lung diseases.

Keywords

single-cell RNA sequencing (scRNA-seq) aging pulmonary alveolar stem cells inflammation response lipid metabolism 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (81430001 and 81870056) and Beijing Major Science and Technology Projects (Z171100000417003 to N.T.).

Supplementary material

11427_2019_9583_MOESM1_ESM.pdf (397 kb)
Supplementary material, approximately 228 KB.

References

  1. Anderson, R.M., Shanmuganayagam, D., and Weindruch, R. (2009). Caloric restriction and aging: studies in mice and monkeys. Toxicol Pathol 37, 47–51.CrossRefPubMedGoogle Scholar
  2. Angelidis, I., Simon, L.M., Fernandez, I.E., Strunz, M., Mayr, C.H., Greiffo, F.R., Tsitsiridis, G., Ansari, M., Graf, E., Strom, T.M., et al. (2019). An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics. Nat Commun 10, 963.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Barkauskas, C.E., Cronce, M.J., Rackley, C.R., Bowie, E.J., Keene, D.R., Stripp, B.R., Randell, S.H., Noble, P.W., and Hogan, B.L.M. (2013). Type 2 alveolar cells are stem cells in adult lung. J Clin Invest 123, 3025–3036.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bauer, Y., Tedrow, J., de Bernard, S., Birker-Robaczewska, M., Gibson, K. F., Guardela, B.J., Hess, P., Klenk, A., Lindell, K.O., Poirey, S., et al. (2015). A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 52, 217–231.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Chan, Y.R., Liu, J.S., Pociask, D.A., Zheng, M., Mietzner, T.A., Berger, T., Mak, T.W., Clifton, M.C., Strong, R.K., Ray, P., et al. (2009). Lipocalin 2 is required for pulmonary host defense against Klebsiella infection. J Immunol 182, 4947–4956.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Desai, T.J., Brownfield, D.G., and Krasnow, M.A. (2014). Alveolar progenitor and stem cells in lung development, renewal and cancer. Nature 507, 190–194.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Fuentes, D., Fernández, N., García, Y., García, T., Morales, A.R., and Menéndez, R. (2018). Age-related changes in the behavior of apolipoprotein E knockout mice. Behaval Sci 8, 33.CrossRefGoogle Scholar
  8. Georgieva, M., and Stoilov, L. (2008). Assessment of DNA strand breaks induced by bleomycin in barley by the comet assay. Environ Mol Mutagen 49, 381–387.CrossRefPubMedGoogle Scholar
  9. Guglani, L., Gopal, R., Rangel-Moreno, J., Junecko, B.F., Lin, Y., Berger, T., Mak, T.W., Alcorn, J.F., Randall, T.D., Reinhart, T.A., et al. (2012). Lipocalin 2 regulates inflammation during pulmonary mycobacterial infections. PLoS ONE 7, e50052.Google Scholar
  10. Kuhn, C. 3rd. (1968). Cytochemistry of pulmonary alveolar epithelial cells. Am J Pathol 53, 809–833.PubMedPubMedCentralGoogle Scholar
  11. Muzumdar, M.D., Tasic, B., Miyamichi, K., Li, L., and Luo, L. (2007). A global double-fluorescent Cre reporter mouse. Genesis 45, 593–605.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Nalysnyk, L., Cid-Ruzafa, J., Rotella, P., and Esser, D. (2012). Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur Respir Rev 21, 355–361.CrossRefGoogle Scholar
  13. Navarro, S., and Driscoll, B. (2017). Regeneration of the aging lung: a mini-review. Gerontology 63, 270–280.CrossRefPubMedGoogle Scholar
  14. Olajuyin, A.M., Zhang, X., and Ji, H.L. (2019). Alveolar type 2 progenitor cells for lung injury repair. Cell Death Discov 5, 63.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Ouyang, Q., Huang, Z., Lin, H., Ni, J., Lu, H., Chen, X., Wang, Z., and Lin, L. (2015). Apolipoprotein E deficiency and high-fat diet cooperate to trigger lipidosis and inflammation in the lung via the toll-like receptor 4 pathway. Mol Med Rep 12, 2589–2597.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Panda, A., Arjona, A., Sapey, E., Bai, F., Fikrig, E., Montgomery, R.R., Lord, J.M., and Shaw, A.C. (2009). Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol 30, 325–333.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Raghu, G., Weycker, D., Edelsberg, J., Bradford, W.Z., and Oster, G. (2006). Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 174, 810–816.CrossRefPubMedGoogle Scholar
  18. Rock, J.R., Barkauskas, C.E., Cronce, M.J., Xue, Y., Harris, J.R., Liang, J., Noble, P.W., and Hogan, B.L.M. (2011). Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition. Proc Natl Acad Sci USA 108, E1475–E1483.CrossRefPubMedGoogle Scholar
  19. Vockeroth, D., Gunasekara, L., Amrein, M., Possmayer, F., Lewis, J.F., and Veldhuizen, R.A.W. (2010). Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury. Am J Physiol-Lung Cell Mol Physiol 298, L117–L125.CrossRefPubMedGoogle Scholar
  20. Wan, Q., Liu, Z.Y., Yang, Y.P., and Liu, S.M. (2017). Effect of curcumin on inhibiting atherogenesis by down-regulating lipocalin-2 expression in apolipoprotein E knockout mice. Biomed Mater Eng 27, 577–587.Google Scholar
  21. Wang, C., Xu, J., Yang, L., Xu, Y., Zhang, X., Bai, C., Kang, J., Ran, P., Shen, H., Wen, F., et al. (2018). Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study. Lancet 391, 1706–1717.CrossRefPubMedGoogle Scholar
  22. Wang, Y., Tang, Z., Huang, H., Li, J., Wang, Z., Yu, Y., Zhang, C., Li, J., Dai, H., Wang, F., et al. (2018). Pulmonary alveolar type I cell population consists of two distinct subtypes that differ in cell fate. Proc Natl Acad Sci USA 115, 2407–2412.CrossRefPubMedGoogle Scholar
  23. Weyand, C.M., and Goronzy, J.J. (2016). Aging of the immune system. mechanisms and therapeutic targets. Ann Am Thorac Soc 13, S422–S428.Google Scholar
  24. Xia, S., Zhang, X., Zheng, S., Khanabdali, R., Kalionis, B., Wu, J., Wan, W., and Tai, X. (2016). An update on inflamm-aging: mechanisms, prevention, and treatment. J Immunol Res 2016(1), 1–12.CrossRefGoogle Scholar
  25. Xie, T., Wang, Y., Deng, N., Huang, G., Taghavifar, F., Geng, Y., Liu, N., Kulur, V., Yao, C., Chen, P., et al. (2018). Single-cell deconvolution of fibroblast heterogeneity in mouse pulmonary fibrosis. Cell Rep 22, 3625–3640.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Yao, X., Gordon, E.M., Figueroa, D.M., Barochia, A.V., and Levine, S.J. (2016). Emerging roles of apolipoprotein E and apolipoprotein A-I in the pathogenesis and treatment of lung disease. Am J Respir Cell Mol Biol 55, 159–169.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pulmonary and Critical Care Medicine; Center of Respiratory Medicine, China-Japan Friendship Hospital; National Clinical Research Center for Respiratory DiseasesInstitute of Respiratory Medicine Chinese Academy of Medical SciencesBeijingChina
  2. 2.Graduate School of Peking Union Medical CollegeChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
  3. 3.National Institute of Biological SciencesBeijingChina

Personalised recommendations