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

详细信息    查看全文 | 推荐本文 |

英文篇名：Single-cell RNA sequencing profiling of the effects of aging on alveolar stem cells 作者：Tingting ; Lv ; Kewu ; Jiang ; Jiawen ; Wang ; Nan ; Tang ; Huaping ; Dai ; Chen ; Wang 英文作者：Tingting Lv;Kewu Jiang;Jiawen Wang;Nan Tang;Huaping Dai;Chen Wang;Department of Pulmonary and Critical Care Medicine,Center of Respiratory Medicine,China-Japan Friendship Hospital,National Clinical Research Center for Respiratory Diseases,Institute of Respiratory Medicine Chinese Academy of Medical Sciences;Graduate School of Peking Union Medical College,Chinese Academy of Medical Science and Peking Union Medical College;National Institute of Biological Sciences; 英文关键词：single-cell RNA sequencing (scRNA-seq);;aging;;pulmonary alveolar stem cells;;inflammation response;;lipid metabolism 中文刊名：JCXG 英文刊名：中国科学:生命科学(英文版) 机构：Department of Pulmonary and Critical Care Medicine,Center of Respiratory Medicine,China-Japan Friendship Hospital,National Clinical Research Center for Respiratory Diseases,Institute of Respiratory Medicine Chinese Academy of Medical Sciences;Graduate School of Peking Union Medical College,Chinese Academy of Medical Science and Peking Union Medical College;National Institute of Biological Sciences; 出版日期：2019-07-19 14:44 出版单位：Science China(Life Sciences) 年：2019 期：v.62 基金：supported by the National Natural Science Foundation of China (81430001 and 81870056);; Beijing Major Science and Technology Projects (Z171100000417003 to N.T.) 语种：英文; 页：JCXG201908004 页数：10 CN：08 ISSN：11-5841/Q 分类号：40-49

摘要

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.
        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.

引文

Anderson,R.M.,Shanmuganayagam,D.,and Weindruch,R.(2009)Caloric restriction and aging:studies in mice and monkeys.Toxico Pathol 37,47-51.
    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.
    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 1233025-3036.
    Bauer,Y.,Tedrow,J.,de Bernard,S.,Birker-Robaczewska,M.,Gibson,KF.,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 52217-231.
    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).Lipocalin2 is required for pulmonary host defense against Klebsiella infection.JImmunol 182,4947-4956.
    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.
    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.
    Georgieva,M.,and Stoilov,L.(2008).Assessment of DNA strand breaks induced by bleomycin in barley by the comet assay.Environ Mo Mutagen 49,381-387.
    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 mycobacteria infections.PLoS ONE 7,e50052.
    Kuhn,C.3rd.(1968).Cytochemistry of pulmonary alveolar epithelial cells.Am J Pathol 53,809-833.
    Muzumdar,M.D.,Tasic,B.,Miyamichi,K.,Li,L.,and Luo,L.(2007).Aglobal double-fluorescent Cre reporter mouse.Genesis 45,593-605.
    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.
    Navarro,S.,and Driscoll,B.(2017).Regeneration of the aging lung:a mini-review.Gerontology 63,270-280.
    Olajuyin,A.M.,Zhang,X.,and Ji,H.L.(2019).Alveolar type 2 progenitor cells for lung injury repair.Cell Death Discov 5,63.
    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 4pathway.Mol Med Rep 12,2589-2597.
    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.
    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.
    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.
    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 JPhysiol-Lung Cell Mol Physiol 298,L117-L125.
    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.
    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.
    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.
    Weyand,C.M.,and Goronzy,J.J.(2016).Aging of the immune system.mechanisms and therapeutic targets.Ann Am Thorac Soc 13,S422-S428.
    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.
    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.
    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.