Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects

Mertens J, Paquola ACM, Ku M, Hatch E, Boehnke L, Ladjevardi S, Mcgrath S, Campbell B, Lee H, Herdy JR, Goncalves JT, Toda T, Kim Y, Winkler J, Yao J, Hetzer MW, Gage FH (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Cell Stem Cell Elsevier (Cell Press)

Book Volume: 17

Pages Range: 705-18

Journal Issue: 6

DOI: 10.1016/j.stem.2015.09.001

Abstract

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.

Authors with CRIS profile

Tomohisa Toda
Jürgen Winkler Professur für Molekulare Neurologie

Involved external institutions

Salk Institute for Biological Studies US United States (USA) (US) Tsinghua University CN China (CN)

How to cite

APA:

Mertens, J., Paquola, A.C.M., Ku, M., Hatch, E., Boehnke, 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, 17(6), 705-18. https://doi.org/10.1016/j.stem.2015.09.001

MLA:

Mertens, Jerome, et al. "Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects." Cell Stem Cell 17.6 (2015): 705-18.

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