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

Publication ,  Journal Article
Mertens, J; Paquola, ACM; Ku, M; Hatch, E; Böhnke, L; Ladjevardi, S; McGrath, S; Campbell, B; Lee, H; Herdy, JR; Gonçalves, JT; Toda, T ...
Published in: Cell Stem Cell
December 2015

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.

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Published In

Cell Stem Cell

DOI

EISSN

1875-9777

ISSN

1934-5909

Publication Date

December 2015

Volume

17

Issue

6

Start / End Page

705 / 718

Related Subject Headings

  • ran GTP-Binding Protein
  • Young Adult
  • Transcriptome
  • Neurons
  • Neural Cell Adhesion Molecules
  • Middle Aged
  • Infant, Newborn
  • Infant
  • Induced Pluripotent Stem Cells
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
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, 17(6), 705–718. https://doi.org/10.1016/j.stem.2015.09.001
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 17, no. 6 (December 2015): 705–18. https://doi.org/10.1016/j.stem.2015.09.001.
Mertens J, Paquola ACM, Ku M, Hatch E, Böhnke L, Ladjevardi S, et al. Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects. Cell Stem Cell. 2015 Dec;17(6):705–18.
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, Dec. 2015, pp. 705–18. Epmc, doi:10.1016/j.stem.2015.09.001.
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 MW, Gage FH. Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects. Cell Stem Cell. 2015 Dec;17(6):705–718.
Journal cover image

Published In

Cell Stem Cell

DOI

EISSN

1875-9777

ISSN

1934-5909

Publication Date

December 2015

Volume

17

Issue

6

Start / End Page

705 / 718

Related Subject Headings

  • ran GTP-Binding Protein
  • Young Adult
  • Transcriptome
  • Neurons
  • Neural Cell Adhesion Molecules
  • Middle Aged
  • Infant, Newborn
  • Infant
  • Induced Pluripotent Stem Cells
  • Humans