--- _id: '11079' abstract: - lang: eng text: Aging is a major risk factor for many human diseases, and in vitro generation of human neurons is an attractive approach for modeling aging-related brain disorders. However, modeling aging in differentiated human neurons has proved challenging. We generated neurons from human donors across a broad range of ages, either by iPSC-based reprogramming and differentiation or by direct conversion into induced neurons (iNs). While iPSCs and derived neurons did not retain aging-associated gene signatures, iNs displayed age-specific transcriptional profiles and revealed age-associated decreases in the nuclear transport receptor RanBP17. We detected an age-dependent loss of nucleocytoplasmic compartmentalization (NCC) in donor fibroblasts and corresponding iNs and found that reduced RanBP17 impaired NCC in young cells, while iPSC rejuvenation restored NCC in aged cells. These results show that iNs retain important aging-related signatures, thus allowing modeling of the aging process in vitro, and they identify impaired NCC as an important factor in human aging. article_processing_charge: No article_type: original author: - first_name: Jerome full_name: Mertens, Jerome last_name: Mertens - first_name: Apuã C.M. full_name: Paquola, Apuã C.M. last_name: Paquola - first_name: Manching full_name: Ku, Manching last_name: Ku - first_name: Emily full_name: Hatch, Emily last_name: Hatch - first_name: Lena full_name: Böhnke, Lena last_name: Böhnke - first_name: Shauheen full_name: Ladjevardi, Shauheen last_name: Ladjevardi - first_name: Sean full_name: McGrath, Sean last_name: McGrath - first_name: Benjamin full_name: Campbell, Benjamin last_name: Campbell - first_name: Hyungjun full_name: Lee, Hyungjun last_name: Lee - first_name: Joseph R. full_name: Herdy, Joseph R. last_name: Herdy - first_name: J. Tiago full_name: Gonçalves, J. Tiago last_name: Gonçalves - first_name: Tomohisa full_name: Toda, Tomohisa last_name: Toda - first_name: Yongsung full_name: Kim, Yongsung last_name: Kim - first_name: Jürgen full_name: Winkler, Jürgen last_name: Winkler - first_name: Jun full_name: Yao, Jun last_name: Yao - first_name: Martin W full_name: HETZER, Martin W id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed last_name: HETZER orcid: 0000-0002-2111-992X - first_name: Fred H. full_name: Gage, Fred H. last_name: Gage citation: ama: Mertens J, Paquola ACM, Ku M, et al. Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell. 2015;17(6):705-718. doi:10.1016/j.stem.2015.09.001 apa: Mertens, J., Paquola, A. C. M., Ku, M., Hatch, E., Böhnke, L., Ladjevardi, S., … Gage, F. H. (2015). Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell. Elsevier. https://doi.org/10.1016/j.stem.2015.09.001 chicago: Mertens, Jerome, Apuã C.M. Paquola, Manching Ku, Emily Hatch, Lena Böhnke, Shauheen Ladjevardi, Sean McGrath, et al. “Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects.” Cell Stem Cell. Elsevier, 2015. https://doi.org/10.1016/j.stem.2015.09.001. ieee: J. Mertens et al., “Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects,” Cell Stem Cell, vol. 17, no. 6. Elsevier, pp. 705–718, 2015. ista: Mertens J, Paquola ACM, Ku M, Hatch E, Böhnke L, Ladjevardi S, McGrath S, Campbell B, Lee H, Herdy JR, Gonçalves JT, Toda T, Kim Y, Winkler J, Yao J, Hetzer M, Gage FH. 2015. Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell. 17(6), 705–718. mla: Mertens, Jerome, et al. “Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects.” Cell Stem Cell, vol. 17, no. 6, Elsevier, 2015, pp. 705–18, doi:10.1016/j.stem.2015.09.001. short: J. Mertens, A.C.M. Paquola, M. Ku, E. Hatch, L. Böhnke, S. Ladjevardi, S. McGrath, B. Campbell, H. Lee, J.R. Herdy, J.T. Gonçalves, T. Toda, Y. Kim, J. Winkler, J. Yao, M. Hetzer, F.H. Gage, Cell Stem Cell 17 (2015) 705–718. date_created: 2022-04-07T07:49:51Z date_published: 2015-12-03T00:00:00Z date_updated: 2022-07-18T08:44:21Z day: '03' doi: 10.1016/j.stem.2015.09.001 extern: '1' external_id: pmid: - '26456686' intvolume: ' 17' issue: '6' keyword: - Cell Biology - Genetics - Molecular Medicine language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.stem.2015.09.001 month: '12' oa: 1 oa_version: Published Version page: 705-718 pmid: 1 publication: Cell Stem Cell publication_identifier: issn: - 1934-5909 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects type: journal_article user_id: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd volume: 17 year: '2015' ...