A single-cell transcriptomic atlas characterizes ageing tissues in the mouse

被引：704

作者：

Almanzar, Nicole ^{[1
]}

Antony, Jane ^{[2
]}

Baghel, Ankit S. ^{[2
]}

Bakerman, Isaac ^{[2
,3
,4
]}

Bansal, Ishita ^{[2
]}

Barres, Ben A. ^{[5
]}

Beachy, Philip A. ^{[2
,6
,7
,8
]}

Berdnik, Daniela ^{[9
]}

Bilen, Biter ^{[10
]}

Brownfield, Douglas ^{[6
]}

Cain, Corey ^{[11
]}

Chan, Charles K. F. ^{[12
]}

Chen, Michelle B. ^{[13
]}

Clarke, Michael F. ^{[2
]}

Conley, Stephanie D. ^{[14
]}

Darmanis, Spyros ^{[14
]}

Demers, Aaron ^{[14
]}

Demir, Kubilay ^{[2
,7
]}

De Morree, Antoine ^{[10
]}

du Bois, Tessa Divita Haley ^{[9
]}

Ebadi, Hamid ^{[4
]}

Espinoza, F. Hernan ^{[6
]}

Fish, Matt ^{[2
,7
,8
]}

Gan, Qiang ^{[10
]}

George, Benson M. ^{[2
]}

Gillich, Astrid ^{[6
]}

Gomez-Sjoberg, Rafael ^{[14
]}

Green, Foad ^{[14
]}

Genetiano, Geraldine ^{[14
]}

Gu, Xueying ^{[6
]}

Gulati, Gunsagar S. ^{[2
]}

Hahn, Oliver ^{[10
]}

Haney, Michael Seamus ^{[10
]}

Hang, Yan ^{[8
]}

Harris, Lincoln ^{[14
]}

He, Mu ^{[15
]}

Hosseinzadeh, Shayan ^{[14
]}

Huang, Albin ^{[10
]}

Huang, Kerwyn Casey ^{[13
,14
]}

Iram, Tal ^{[10
]}

Isobe, Taichi ^{[2
]}

Ives, Feather ^{[14
]}

Jones, Robert C. ^{[13
]}

Kao, Kevin S. ^{[2
]}

Karkanias, Jim ^{[14
]}

Karnam, Guruswamy ^{[17
,18
]}

Keller, Andreas ^{[10
,19
]}

Kershner, Aaron M. ^{[2
]}

Khoury, Nathalie ^{[10
]}

Kim, Seung K. ^{[6
,20
,21
]}

机构：

[1] Stanford Univ, Sch Med, Dept Pediat Pulm Med, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Stanford Cardiovasc Inst, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA

[5] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA

[6] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA

[7] Howard Hughes Med Inst, Chevy Chase, MD USA

[8] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA

[9] Vet Adm Palo Alto Healthcare Syst, Palo Alto, CA USA

[10] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA

[11] Vet Adm Palo Alto Healthcare Syst, Flow Cytometry Core, Palo Alto, CA USA

[12] Stanford Univ, Div Plast & Reconstruct Surg, Dept Surg, Stanford, CA 94305 USA

[13] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA

[14] Chan Zuckerberg Biohub, San Francisco, CA USA

[15] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA

[16] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA

[17] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[18] Univ Calif San Francisco, Ctr Liver, San Francisco, CA 94143 USA

[19] Saarland Univ, Clin Bioinformat, Saarbrucken, Germany

[20] Stanford Univ, Dept Med, Stanford, CA 94305 USA

[21] Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA

[22] Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA

[23] Stanford Univ, Sean N Parker Ctr Asthma & Allergy Res, Sch Med, Stanford, CA 94305 USA

[24] Stanford Univ, Div Pulm & Crit Care, Dept Med, Sch Med, Stanford, CA 94305 USA

[25] Stanford Univ, Sch Med, Dept Dev Biol, Pittsburgh, PA USA

[26] Vet Adm Palo Alto Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Palo Alto, CA USA

[27] Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA

[28] Stanford Univ, Vera Moulton Wall Ctr Pulm & Vasc Dis, Sch Med, Stanford, CA 94305 USA

[29] Stanford Univ, Sch Med, Div Cardiol, Dept Pediat, Stanford, CA 94305 USA

[30] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[31] Stanford Univ, Paul F Glenn Ctr Biol Aging, Sch Med, Stanford, CA 94305 USA

[32] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA

[33] Stanford Univ, Ludwig Ctr Canc Stem Cell Res & Med, Sch Med, Stanford, CA 94305 USA

[34] Stanford Univ, Stanford Canc Inst, Sch Med, Stanford, CA 94305 USA

[35] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Med Biotechnol, Krakow, Poland

[36] Stanford Univ, Wu Tsai Neurosci Inst, Sch Med, Stanford, CA 94305 USA

[37] Stanford Univ, Dept Elect Engn, Palo Alto, CA 94304 USA

[38] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[39] Stanford Univ, Dept Biomed Data Sci, Palo Alto, CA 94304 USA

[40] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands

[41] Univ British Columbia, Sch Biomed Engn, Vancouver, BC, Canada

[42] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC, Canada

[43] Canadian Inst Adv Res, Humans & Microbiome Program, Toronto, ON, Canada

来源：

NATURE | 2020年 / 583卷 / 7817期

基金：

美国国家卫生研究院;

关键词：

GENE-EXPRESSION; SENESCENCE; FRAMEWORK; BLADDER; PROMOTES; CANCER; BRAIN;

D O I：

10.1038/s41586-020-2496-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Ageing is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death(1). Despite rapid advances over recent years, many of the molecular and cellular processes that underlie the progressive loss of healthy physiology are poorly understood(2). To gain a better insight into these processes, here we generate a single-cell transcriptomic atlas across the lifespan of Mus musculus that includes data from 23 tissues and organs. We found cell-specific changes occurring across multiple cell types and organs, as well as age-related changes in the cellular composition of different organs. Using single-cell transcriptomic data, we assessed cell-type-specific manifestations of different hallmarks of ageing-such as senescence(3), genomic instability(4) and changes in the immune system(2). This transcriptomic atlas-which we denote Tabula Muris Senis, or 'Mouse Ageing Cell Atlas'-provides molecular information about how the most important hallmarks of ageing are reflected in a broad range of tissues and cell types.

引用

页码：590 / +

页数：28

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