Single-Cell Analysis of Human Pancreas Reveals Transcriptional Signatures of Aging and Somatic Mutation Patterns
As organisms age, cells accumulate genetic and epigenetic errors that eventually lead to impaired organ function or catastrophic transformation such as cancer. Because aging reflects a stochastic process of increasing disorder, cells in an organ will be individually affected in different ways, thus...
Uložené v:
| Vydané v: | Cell Ročník 171; číslo 2; s. 321 |
|---|---|
| Hlavní autori: | , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
United States
05.10.2017
|
| Predmet: | |
| ISSN: | 1097-4172, 1097-4172 |
| On-line prístup: | Zistit podrobnosti o prístupe |
| Tagy: |
Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
|
| Abstract | As organisms age, cells accumulate genetic and epigenetic errors that eventually lead to impaired organ function or catastrophic transformation such as cancer. Because aging reflects a stochastic process of increasing disorder, cells in an organ will be individually affected in different ways, thus rendering bulk analyses of postmitotic adult cells difficult to interpret. Here, we directly measure the effects of aging in human tissue by performing single-cell transcriptome analysis of 2,544 human pancreas cells from eight donors spanning six decades of life. We find that islet endocrine cells from older donors display increased levels of transcriptional noise and potential fate drift. By determining the mutational history of individual cells, we uncover a novel mutational signature in healthy aging endocrine cells. Our results demonstrate the feasibility of using single-cell RNA sequencing (RNA-seq) data from primary cells to derive insights into genetic and transcriptional processes that operate on aging human tissue. |
|---|---|
| AbstractList | As organisms age, cells accumulate genetic and epigenetic errors that eventually lead to impaired organ function or catastrophic transformation such as cancer. Because aging reflects a stochastic process of increasing disorder, cells in an organ will be individually affected in different ways, thus rendering bulk analyses of postmitotic adult cells difficult to interpret. Here, we directly measure the effects of aging in human tissue by performing single-cell transcriptome analysis of 2,544 human pancreas cells from eight donors spanning six decades of life. We find that islet endocrine cells from older donors display increased levels of transcriptional noise and potential fate drift. By determining the mutational history of individual cells, we uncover a novel mutational signature in healthy aging endocrine cells. Our results demonstrate the feasibility of using single-cell RNA sequencing (RNA-seq) data from primary cells to derive insights into genetic and transcriptional processes that operate on aging human tissue. As organisms age, cells accumulate genetic and epigenetic errors that eventually lead to impaired organ function or catastrophic transformation such as cancer. Because aging reflects a stochastic process of increasing disorder, cells in an organ will be individually affected in different ways, thus rendering bulk analyses of postmitotic adult cells difficult to interpret. Here, we directly measure the effects of aging in human tissue by performing single-cell transcriptome analysis of 2,544 human pancreas cells from eight donors spanning six decades of life. We find that islet endocrine cells from older donors display increased levels of transcriptional noise and potential fate drift. By determining the mutational history of individual cells, we uncover a novel mutational signature in healthy aging endocrine cells. Our results demonstrate the feasibility of using single-cell RNA sequencing (RNA-seq) data from primary cells to derive insights into genetic and transcriptional processes that operate on aging human tissue.As organisms age, cells accumulate genetic and epigenetic errors that eventually lead to impaired organ function or catastrophic transformation such as cancer. Because aging reflects a stochastic process of increasing disorder, cells in an organ will be individually affected in different ways, thus rendering bulk analyses of postmitotic adult cells difficult to interpret. Here, we directly measure the effects of aging in human tissue by performing single-cell transcriptome analysis of 2,544 human pancreas cells from eight donors spanning six decades of life. We find that islet endocrine cells from older donors display increased levels of transcriptional noise and potential fate drift. By determining the mutational history of individual cells, we uncover a novel mutational signature in healthy aging endocrine cells. Our results demonstrate the feasibility of using single-cell RNA sequencing (RNA-seq) data from primary cells to derive insights into genetic and transcriptional processes that operate on aging human tissue. |
| Author | Beausang, John Mignardi, Marco Quake, Stephen R Enge, Martin Bottino, Rita Arda, H Efsun Kim, Seung K |
| Author_xml | – sequence: 1 givenname: Martin surname: Enge fullname: Enge, Martin organization: Department of Bioengineering and Applied Physics, Stanford University, Stanford, CA 94305, USA – sequence: 2 givenname: H Efsun surname: Arda fullname: Arda, H Efsun organization: Department of Developmental Biology, Stanford University School of Medicine, CA 94305, USA – sequence: 3 givenname: Marco surname: Mignardi fullname: Mignardi, Marco organization: Department of Bioengineering and Applied Physics, Stanford University, Stanford, CA 94305, USA; Department of Information Technology, Uppsala University, Sweden and SciLifeLab, Uppsala, Sweden SE-751 05 – sequence: 4 givenname: John surname: Beausang fullname: Beausang, John organization: Department of Bioengineering and Applied Physics, Stanford University, Stanford, CA 94305, USA – sequence: 5 givenname: Rita surname: Bottino fullname: Bottino, Rita organization: Institute of Cellular Therapeutics, Allegheny Health Network, 320 East North Avenue, Pittsburgh, PA 15212, USA – sequence: 6 givenname: Seung K surname: Kim fullname: Kim, Seung K organization: Department of Developmental Biology, Stanford University School of Medicine, CA 94305, USA – sequence: 7 givenname: Stephen R surname: Quake fullname: Quake, Stephen R email: quake@stanford.edu organization: Department of Bioengineering and Applied Physics, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Institute of Cellular Therapeutics, Allegheny Health Network, 320 East North Avenue, Pittsburgh, PA 15212, USA. Electronic address: quake@stanford.edu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28965763$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkMlOwzAURS1URAf4ARbISzYJz66HZFlVQJGKQLSsI8dxKleJU2wHqX9PyiCxum9x3tHVnaKR65xB6JpASoCIu32qTdOkFIhMIU8B2BmaEMhlwoiko3_3GE1D2ANAxjm_QGOa5YJLMZ-gw8a6XWOS5WDCC6eaY7ABdzVe9a1y-FU57Y0K-M18GtUEvPXKBe3tIdpuoPHG7pyKvTffT4vdYMPKVXjTtSpajZ_7qE7oYIrReBcu0Xk9iMzVb87Q-8P9drlK1i-PT8vFOtGC5jGhQA1wAhUZ-hsKJdFUirzMGamZ0VoqQao5VJwxMARYBULMM65LXWcKlKIzdPvjPfjuozchFq0Np72UM10fCpIzLonkkg_ozS_al62pioO3rfLH4m8l-gU74Wzf |
| CitedBy_id | crossref_primary_10_1007_s10522_023_10084_5 crossref_primary_10_1073_pnas_1907883116 crossref_primary_10_1016_j_molimm_2018_11_007 crossref_primary_10_1038_s41580_019_0204_5 crossref_primary_10_1146_annurev_immunol_110519_071134 crossref_primary_10_1038_s41556_019_0446_7 crossref_primary_10_1053_j_gastro_2020_11_010 crossref_primary_10_1111_acel_13042 crossref_primary_10_3389_fendo_2021_736286 crossref_primary_10_3389_fendo_2023_1212716 crossref_primary_10_1016_j_molcel_2020_12_018 crossref_primary_10_1038_s41593_019_0491_3 crossref_primary_10_15252_embj_2020106825 crossref_primary_10_1038_s41598_020_60998_0 crossref_primary_10_1016_j_isci_2023_106439 crossref_primary_10_1161_ATVBAHA_124_321781 crossref_primary_10_1016_j_tcb_2023_07_004 crossref_primary_10_1101_gr_278144_123 crossref_primary_10_1016_j_bpj_2025_07_043 crossref_primary_10_1038_s41598_020_57903_0 crossref_primary_10_1038_s41467_022_28020_5 crossref_primary_10_1111_acel_13712 crossref_primary_10_1093_nar_gkac392 crossref_primary_10_1186_s12915_025_02390_w crossref_primary_10_1186_s13059_021_02452_6 crossref_primary_10_1016_j_jid_2020_11_018 crossref_primary_10_1038_s41467_022_32869_x crossref_primary_10_1111_ene_14294 crossref_primary_10_1007_s00018_020_03731_4 crossref_primary_10_1002_advs_202304084 crossref_primary_10_1016_j_pbiomolbio_2023_01_001 crossref_primary_10_1016_j_celrep_2024_114047 crossref_primary_10_1038_s41467_024_49921_7 crossref_primary_10_1210_jc_2018_00791 crossref_primary_10_1016_j_cell_2024_01_021 crossref_primary_10_1038_s41590_023_01452_x crossref_primary_10_1146_annurev_biodatasci_020722_120642 crossref_primary_10_1007_s12035_020_02240_6 crossref_primary_10_1038_s41467_025_61403_y crossref_primary_10_1016_j_compbiomed_2025_110332 crossref_primary_10_1016_j_yexcr_2019_111613 crossref_primary_10_1016_j_isci_2024_110644 crossref_primary_10_1038_s41392_023_01528_y crossref_primary_10_1016_j_stem_2021_03_005 crossref_primary_10_2174_0118740707311249240604053619 crossref_primary_10_1016_j_tcb_2022_09_005 crossref_primary_10_1186_s13059_022_02820_w crossref_primary_10_1007_s00125_018_4639_6 crossref_primary_10_1016_j_jhep_2024_03_043 crossref_primary_10_1016_j_mce_2021_111459 crossref_primary_10_1038_s41592_019_0372_4 crossref_primary_10_1016_j_gpb_2023_06_003 crossref_primary_10_1016_j_gde_2023_102099 crossref_primary_10_1016_j_mad_2020_111247 crossref_primary_10_1038_s41467_024_55415_3 crossref_primary_10_1259_bjr_20190198 crossref_primary_10_1210_clinem_dgab147 crossref_primary_10_1016_j_ddmod_2019_01_001 crossref_primary_10_3389_fendo_2025_1548596 crossref_primary_10_1017_S0007114521004001 crossref_primary_10_1186_s13024_018_0284_2 crossref_primary_10_1210_endocr_bqac156 crossref_primary_10_1038_s41588_021_00921_z crossref_primary_10_1016_j_cmet_2017_11_009 crossref_primary_10_3390_cancers13195027 crossref_primary_10_1053_j_gastro_2023_01_028 crossref_primary_10_1016_j_cell_2020_01_009 crossref_primary_10_1007_s00401_018_1850_y crossref_primary_10_1016_j_mad_2024_111951 crossref_primary_10_1093_bib_bbad332 crossref_primary_10_1093_bib_bbac241 crossref_primary_10_1101_gad_351728_124 crossref_primary_10_3389_fvets_2021_660435 crossref_primary_10_1038_s42003_024_06111_x crossref_primary_10_1126_science_abq7871 crossref_primary_10_7554_eLife_67437 crossref_primary_10_3389_fendo_2025_1612576 crossref_primary_10_1158_2159_8290_CD_20_1202 crossref_primary_10_3389_fcell_2020_593007 crossref_primary_10_2337_dbi21_0008 crossref_primary_10_1038_s41580_018_0020_3 crossref_primary_10_2337_dbi18_0019 crossref_primary_10_1007_s11357_021_00339_9 crossref_primary_10_3389_fbinf_2025_1657895 crossref_primary_10_4093_dmj_2022_0324 crossref_primary_10_1038_s41586_020_2888_2 crossref_primary_10_1146_annurev_genom_121520_081242 crossref_primary_10_1038_s43587_024_00613_3 crossref_primary_10_1101_gr_253880_119 crossref_primary_10_1101_gr_275569_121 crossref_primary_10_1016_j_celrep_2025_115781 crossref_primary_10_1111_acel_13946 crossref_primary_10_1186_s11658_018_0118_9 crossref_primary_10_1242_dev_200167 crossref_primary_10_1016_j_arr_2024_102268 crossref_primary_10_1038_s41467_025_57286_8 crossref_primary_10_1038_s43587_022_00335_4 crossref_primary_10_1016_j_tem_2018_10_002 crossref_primary_10_1038_s42003_024_05877_4 crossref_primary_10_1016_j_cmet_2021_05_015 crossref_primary_10_1038_s43587_024_00588_1 crossref_primary_10_1093_bib_bbae047 crossref_primary_10_1159_000509864 crossref_primary_10_1016_j_envres_2025_120752 crossref_primary_10_1016_j_bbadis_2018_01_026 crossref_primary_10_1093_bib_bbaa360 crossref_primary_10_1210_endrev_bnab010 crossref_primary_10_2337_db20_1115 crossref_primary_10_3390_biom10121681 crossref_primary_10_1007_s12539_023_00587_7 crossref_primary_10_1016_j_cell_2020_07_017 crossref_primary_10_1038_s41598_018_35218_5 crossref_primary_10_1016_j_cels_2018_07_007 crossref_primary_10_1186_s13059_023_03007_7 crossref_primary_10_1073_pnas_1922388117 crossref_primary_10_1038_s41598_024_54798_z crossref_primary_10_1038_s41467_020_15997_0 crossref_primary_10_1146_annurev_pharmtox_033123_123610 crossref_primary_10_1093_molbev_msab302 crossref_primary_10_1007_s00125_022_05699_1 crossref_primary_10_1016_j_isci_2023_106368 crossref_primary_10_1002_gepi_22209 crossref_primary_10_1093_nar_gky856 crossref_primary_10_1146_annurev_genet_120417_031534 crossref_primary_10_1186_s13059_020_02006_2 crossref_primary_10_3389_fendo_2023_1196460 crossref_primary_10_1002_cso2_1045 crossref_primary_10_1210_endrev_bnaa032 crossref_primary_10_7554_eLife_95720 crossref_primary_10_1016_j_stem_2024_04_010 crossref_primary_10_1038_s41467_020_18581_8 crossref_primary_10_3389_fimmu_2021_751701 crossref_primary_10_1016_j_metabol_2024_156042 crossref_primary_10_1038_s41581_024_00849_7 crossref_primary_10_3390_genes11070792 crossref_primary_10_1515_hsz_2018_0449 crossref_primary_10_1042_BCJ20210547 crossref_primary_10_1080_19382014_2024_2339558 crossref_primary_10_1038_s10038_020_00844_3 crossref_primary_10_1016_j_molmet_2023_101678 crossref_primary_10_1038_s42255_023_00876_x crossref_primary_10_3389_fgene_2019_00629 crossref_primary_10_1016_j_ddmod_2019_03_003 crossref_primary_10_1101_gad_342378_120 crossref_primary_10_1186_s13059_025_03679_3 crossref_primary_10_1038_s41582_023_00815_0 crossref_primary_10_7554_eLife_68048 crossref_primary_10_1016_j_molmet_2022_101595 crossref_primary_10_1158_0008_5472_CAN_21_0427 crossref_primary_10_1186_s12864_024_10160_1 crossref_primary_10_1051_bioconf_202414203002 crossref_primary_10_1007_s00125_023_06033_z crossref_primary_10_1016_j_cmet_2021_01_016 crossref_primary_10_1038_s41591_021_01645_7 crossref_primary_10_1038_s41467_022_28655_4 crossref_primary_10_1038_s43587_022_00198_9 crossref_primary_10_1136_gutjnl_2022_329313 crossref_primary_10_1186_s12933_025_02865_8 crossref_primary_10_1038_s41586_025_09435_8 crossref_primary_10_1093_nargab_lqad068 crossref_primary_10_3390_genes13061015 crossref_primary_10_1016_j_cmet_2020_04_005 crossref_primary_10_1016_j_ejcb_2023_151340 crossref_primary_10_1214_19_STS7560 crossref_primary_10_3390_ijms24043701 crossref_primary_10_1002_ijc_35456 crossref_primary_10_1126_science_abn7113 crossref_primary_10_1016_j_ceb_2018_05_016 crossref_primary_10_7554_eLife_80380 crossref_primary_10_34133_research_0743 crossref_primary_10_1186_s13073_023_01179_2 crossref_primary_10_1038_s41467_019_13192_4 crossref_primary_10_1007_s00335_020_09834_4 crossref_primary_10_1016_j_cmet_2019_01_021 crossref_primary_10_1073_pnas_1918314117 crossref_primary_10_1016_j_cmet_2023_10_001 crossref_primary_10_1016_j_celrep_2025_115935 crossref_primary_10_1210_endocr_bqae078 crossref_primary_10_1038_s41467_019_11181_1 crossref_primary_10_1007_s10489_022_03440_4 crossref_primary_10_3390_ijms24032943 crossref_primary_10_1007_s00125_022_05662_0 crossref_primary_10_1016_j_ejphar_2025_177867 crossref_primary_10_1038_s42255_020_00304_4 crossref_primary_10_1007_s11357_025_01769_5 crossref_primary_10_1016_j_cobme_2020_06_003 crossref_primary_10_3389_fgene_2023_1029758 crossref_primary_10_3390_nu14112181 crossref_primary_10_1038_s43587_025_00890_6 crossref_primary_10_1111_acel_13316 crossref_primary_10_1016_j_ccell_2023_12_006 crossref_primary_10_1158_2159_8290_CD_19_0094 crossref_primary_10_3390_genes13071176 crossref_primary_10_1038_s42003_022_04242_7 crossref_primary_10_1016_j_arr_2024_102530 crossref_primary_10_1007_s12561_022_09335_9 crossref_primary_10_3389_fnbeh_2020_00096 crossref_primary_10_26508_lsa_202402916 crossref_primary_10_1007_s00439_018_1955_3 crossref_primary_10_1038_s41467_018_06318_7 crossref_primary_10_1155_2021_9982954 crossref_primary_10_1016_j_jmb_2021_167179 crossref_primary_10_1111_1755_0998_14101 crossref_primary_10_1126_science_abm5874 crossref_primary_10_1186_s13059_019_1919_5 crossref_primary_10_1016_j_conb_2020_05_001 crossref_primary_10_3390_genes14061222 crossref_primary_10_3389_fimmu_2025_1534263 crossref_primary_10_1007_s13238_019_0617_0 crossref_primary_10_1016_j_arr_2022_101674 crossref_primary_10_1016_j_csbj_2021_05_046 crossref_primary_10_1016_j_coisb_2019_10_005 crossref_primary_10_1101_gr_279865_124 crossref_primary_10_1186_s40779_024_00537_4 crossref_primary_10_1038_s41586_020_2922_4 crossref_primary_10_1038_s43587_025_00886_2 crossref_primary_10_1146_annurev_genom_120523_024422 crossref_primary_10_3389_fcell_2022_886153 crossref_primary_10_1111_acel_13320 crossref_primary_10_1016_j_ijbiomac_2023_123632 crossref_primary_10_1016_j_cell_2020_02_008 crossref_primary_10_1002_advs_201800672 crossref_primary_10_1016_j_ymeth_2019_11_002 crossref_primary_10_1038_s42255_020_0196_7 crossref_primary_10_1016_j_cell_2020_06_024 crossref_primary_10_1186_s13059_023_03036_2 crossref_primary_10_1038_s41576_019_0130_6 crossref_primary_10_7554_eLife_52580 crossref_primary_10_1007_s12539_023_00601_y crossref_primary_10_1016_j_molmet_2020_101071 crossref_primary_10_1158_2159_8290_CD_23_0013 crossref_primary_10_1038_s41467_025_60694_5 crossref_primary_10_1101_gr_254557_119 crossref_primary_10_1007_s00439_023_02529_1 crossref_primary_10_1016_j_cell_2018_03_079 crossref_primary_10_1038_s41598_020_71805_1 crossref_primary_10_1007_s11892_018_1085_2 crossref_primary_10_1038_s41586_022_04461_2 crossref_primary_10_1002_med_21985 crossref_primary_10_1210_clinem_dgac535 crossref_primary_10_1038_s41467_019_08831_9 crossref_primary_10_1016_j_cmet_2018_11_016 crossref_primary_10_1093_bib_bbad045 crossref_primary_10_1016_j_tem_2021_04_009 crossref_primary_10_14348_molcells_2021_2239 crossref_primary_10_1002_JLB_6MR0320_234R crossref_primary_10_3389_fgene_2022_825896 crossref_primary_10_3390_biology10060503 crossref_primary_10_1056_NEJMra2101920 crossref_primary_10_3390_ijms21218278 crossref_primary_10_1186_s13073_021_00941_8 crossref_primary_10_1186_s12864_024_09964_y crossref_primary_10_1038_s41467_022_33758_z crossref_primary_10_1038_s43587_020_00015_1 crossref_primary_10_1242_dev_168609 crossref_primary_10_1038_s41592_024_02493_2 crossref_primary_10_1161_ATVBAHA_121_316883 crossref_primary_10_1242_dev_179051 crossref_primary_10_1038_s41388_021_02026_7 crossref_primary_10_1016_j_cels_2021_05_006 crossref_primary_10_1038_s41551_021_00757_2 crossref_primary_10_1093_hmg_ddaa024 crossref_primary_10_1038_s41467_022_29588_8 crossref_primary_10_1016_j_celrep_2023_112902 crossref_primary_10_1016_j_jcjd_2021_03_007 crossref_primary_10_1016_j_molmet_2021_101213 crossref_primary_10_3390_ijms22041833 crossref_primary_10_3390_cancers15061807 crossref_primary_10_1038_s42255_020_00295_2 crossref_primary_10_1093_nsr_nwaa127 crossref_primary_10_1016_j_molmet_2020_101057 crossref_primary_10_1016_j_cmet_2023_03_008 crossref_primary_10_1038_s41467_020_19015_1 crossref_primary_10_1161_ATVBAHA_118_310797 crossref_primary_10_1007_s11427_023_2305_0 crossref_primary_10_1016_j_tig_2024_09_006 crossref_primary_10_1016_j_prp_2023_154614 crossref_primary_10_1186_s13059_022_02785_w crossref_primary_10_3389_fnins_2021_638122 crossref_primary_10_3390_life13101988 crossref_primary_10_1093_nar_gky698 crossref_primary_10_3390_cancers15072159 crossref_primary_10_1093_bib_bbad216 crossref_primary_10_1136_gutjnl_2020_322874 crossref_primary_10_3389_fmed_2018_00202 crossref_primary_10_1038_s41467_021_26779_7 crossref_primary_10_1186_s13059_023_03075_9 crossref_primary_10_1093_bib_bbae305 crossref_primary_10_3390_cells11172711 crossref_primary_10_1016_j_jcyt_2020_10_004 crossref_primary_10_1038_s41586_019_1168_5 crossref_primary_10_1038_s41596_018_0073_y crossref_primary_10_1002_bies_202000140 crossref_primary_10_1038_s41586_018_0590_4 crossref_primary_10_1210_endocr_bqac193 crossref_primary_10_1093_bib_bbac167 crossref_primary_10_1186_s13059_019_1863_4 crossref_primary_10_3389_fcell_2021_661105 crossref_primary_10_1038_s41598_018_36289_0 crossref_primary_10_1186_s13073_023_01269_1 crossref_primary_10_1146_annurev_genet_120417_031247 crossref_primary_10_1016_j_pneurobio_2022_102387 crossref_primary_10_1210_jc_2018_01626 crossref_primary_10_1016_j_gpb_2022_12_008 crossref_primary_10_1172_JCI158446 crossref_primary_10_1073_pnas_1902510116 crossref_primary_10_1016_j_biocel_2022_106343 crossref_primary_10_1097_MPA_0000000000001612 crossref_primary_10_1093_bib_bbae572 crossref_primary_10_1007_s11357_024_01113_3 crossref_primary_10_1182_blood_2023022197 crossref_primary_10_1111_1753_0407_13236 crossref_primary_10_1111_acel_14163 crossref_primary_10_1038_s41588_025_02260_9 crossref_primary_10_1093_nar_gkaa1064 crossref_primary_10_1186_s12864_024_10335_w crossref_primary_10_3390_life12091440 crossref_primary_10_1038_s42003_024_06475_0 crossref_primary_10_1053_j_gastro_2020_12_028 crossref_primary_10_1038_s41598_020_79992_7 crossref_primary_10_1016_j_cell_2019_08_006 crossref_primary_10_1371_journal_pone_0249691 crossref_primary_10_3390_cells12010076 crossref_primary_10_1038_s41467_023_41683_y crossref_primary_10_1007_s00018_021_03951_2 crossref_primary_10_1038_s43587_024_00696_y crossref_primary_10_1016_j_tem_2024_01_003 crossref_primary_10_1038_s41467_019_12293_4 crossref_primary_10_1515_mr_2025_0032 |
| ContentType | Journal Article |
| Copyright | Copyright © 2017 Elsevier Inc. All rights reserved. |
| Copyright_xml | – notice: Copyright © 2017 Elsevier Inc. All rights reserved. |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1016/j.cell.2017.09.004 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 1097-4172 |
| ExternalDocumentID | 28965763 |
| Genre | Journal Article |
| GrantInformation_xml | – fundername: NIDDK NIH HHS grantid: UC4 DK104211 – fundername: NIDDK NIH HHS grantid: T32 DK007217 – fundername: NIDDK NIH HHS grantid: P30 DK116074 – fundername: NIDDK NIH HHS grantid: P30 DK020593 – fundername: NHLBI NIH HHS grantid: U01 HL099999 – fundername: NHLBI NIH HHS grantid: U01 HL099995 |
| GroupedDBID | --- --K -DZ -ET -~X 0R~ 0SF 0WA 1RT 1~5 29B 2FS 2WC 3EH 4.4 457 4G. 53G 5GY 5RE 62- 6I. 6J9 7-5 85S AACTN AAEDT AAEDW AAFTH AAFWJ AAHBH AAKRW AAKUH AALRI AAMRU AAVLU AAXUO ABCQX ABJNI ABMAC ABOCM ABVKL ACGFO ACGFS ACNCT ADBBV ADEZE ADVLN AEFWE AENEX AEXQZ AFTJW AGHSJ AGKMS AHHHB AITUG AKAPO AKRWK ALMA_UNASSIGNED_HOLDINGS AMRAJ ASPBG AVWKF AZFZN BAWUL CGR CS3 CUY CVF DIK DU5 E3Z EBS ECM EIF EJD F5P FCP FDB FIRID HH5 IH2 IHE IXB J1W JIG K-O KOO KQ8 L7B LX5 M3Z M41 N9A NCXOZ NPM O-L O9- OK1 P2P RCE RIG RNS ROL RPZ SCP SDG SDP SES SSZ TAE TN5 TR2 TWZ UKR UPT VQA WH7 YZZ ZCA 7X8 AAYWO ABDGV ACVFH ADCNI ADXHL AEUPX AFPUW AIGII AKBMS AKYEP APXCP EFKBS |
| ID | FETCH-LOGICAL-c629t-202e0510d1417e20b1c2769b941f4ecc7a61d30d5440e104d066385cbcf8a0aa2 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 380 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000412346100010&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1097-4172 |
| IngestDate | Sun Sep 28 04:26:58 EDT 2025 Thu Jan 02 22:58:57 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 2 |
| Keywords | insulin mutational signatures human aging transcriptional instability glucagon single-cell RNA-seq islet somatic variation human pancreas |
| Language | English |
| License | Copyright © 2017 Elsevier Inc. All rights reserved. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c629t-202e0510d1417e20b1c2769b941f4ecc7a61d30d5440e104d066385cbcf8a0aa2 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | http://www.cell.com/article/S009286741731053X/pdf |
| PMID | 28965763 |
| PQID | 1945717575 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_1945717575 pubmed_primary_28965763 |
| PublicationCentury | 2000 |
| PublicationDate | 2017-10-05 |
| PublicationDateYYYYMMDD | 2017-10-05 |
| PublicationDate_xml | – month: 10 year: 2017 text: 2017-10-05 day: 05 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Cell |
| PublicationTitleAlternate | Cell |
| PublicationYear | 2017 |
| References | 29211979 - Cell Metab. 2017 Dec 5;26(6):809-811 |
| References_xml | – reference: 29211979 - Cell Metab. 2017 Dec 5;26(6):809-811 |
| SSID | ssj0008555 |
| Score | 2.6686876 |
| Snippet | As organisms age, cells accumulate genetic and epigenetic errors that eventually lead to impaired organ function or catastrophic transformation such as cancer.... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 321 |
| SubjectTerms | Adult Aging - pathology Cellular Senescence Child Child, Preschool Humans Infant Middle Aged Mutation Pancreas - cytology Pancreas - pathology Pancreas - physiology Polymorphism, Single Nucleotide Sequence Analysis, RNA Single-Cell Analysis Transcription, Genetic |
| Title | Single-Cell Analysis of Human Pancreas Reveals Transcriptional Signatures of Aging and Somatic Mutation Patterns |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/28965763 https://www.proquest.com/docview/1945717575 |
| Volume | 171 |
| WOSCitedRecordID | wos000412346100010&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3dS8MwED_UKfji98f8IoKvxTZN0_RJhjh8cGM4lb2VNEllIO2028D_3kvasidB8CVvCeHukvvd5XI_gBuqaBhSKbxcJRigZBizShNLj6skMuieWO5aKb09xcOhmEySUZNwq5qyyvZOdBe1LpXNkd9isB1h6IHo4m726VnWKPu62lBorEMnRChjD2Y8WXULF5FjPbWPrB5DT918mqnru2xi3JZ2xa7PqSNq-wViOlfT3_3vJvdgpwGZpFdbxT6smeIAtmraye9DmI3RX30Y7x73RtquJKTMicvokxEagi1VJ89miTCyIs6ftbcLrjuevtf9QN2knqU5IrLQZFy6_q9ksKjf93El-1eoqI7gtf_wcv_oNcwLnuI0mePRocaeVh2g2Az1s0DRmCdZwoKcodJjyQMd-jpizDeoUG2Bi4hUpnIhfSnpMWwUZWFOgWRBJEIufK4zzTKK6EIIpnKttGaa8aAL160oU7RsqxVZmHJRpSthduGk1kc6q1twpBgmcoyUwrM_zD6HbatmV4EXXUAnR8mZS9hUy_m0-rpyJoPjcDT4AexHy4g |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Single-Cell+Analysis+of+Human+Pancreas+Reveals+Transcriptional+Signatures+of+Aging+and+Somatic+Mutation+Patterns&rft.jtitle=Cell&rft.au=Enge%2C+Martin&rft.au=Arda%2C+H+Efsun&rft.au=Mignardi%2C+Marco&rft.au=Beausang%2C+John&rft.date=2017-10-05&rft.eissn=1097-4172&rft.volume=171&rft.issue=2&rft.spage=321&rft_id=info:doi/10.1016%2Fj.cell.2017.09.004&rft_id=info%3Apmid%2F28965763&rft_id=info%3Apmid%2F28965763&rft.externalDocID=28965763 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1097-4172&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1097-4172&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1097-4172&client=summon |