4.2 Article

Improved Sendai viral system for reprogramming to naive pluripotency

Journal

CELL REPORTS METHODS
Volume 2, Issue 11, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.crmeth.2022.100317

Keywords

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Funding

  1. Core Center for iPS Cell Research, Research Center Network for Realization of Regenerative Medicine, AMED [JP21bm0104001]
  2. iPS Cell Research Fund
  3. JSPS KAKENHI [16K19429, 18K15846]
  4. L. K. Whittier Foundation
  5. Roddenberry Foundation
  6. Gladstone Institutes
  7. National Heart, Lung, and Blood Institute (NHLBI)
  8. National Institutes of Health (NIH) [U01-HL100406, U01-HL098179, R01-HL130533, R01-HL135358]
  9. National Center for Research Resources [RR18928-01]

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This study reports a modified Sendai virus vector system that can generate transgene-free naive human iPSCs with superior differentiation potential. This method is applicable to various cell types and allows for the generation of naive iPSCs in a feeder-free culture, resulting in better differentiation compared to conventional methods.
Naive human induced pluripotent stem cells (iPSCs) can be generated by reprogramming somatic cells with Sendai virus (SeV) vectors. However, only dermal fibroblasts have been successfully reprogrammed this way, and the process requires culture on feeder cells. Moreover, SeV vectors are highly persistent and inhibit subsequent differentiation of iPSCs. Here, we report a modified SeV vector system to generate transgene-free naive human iPSCs with superior differentiation potential. The modified method can be applied not only to fibroblasts but also to other somatic cell types. SeV vectors disappear quickly at early passages, and this approach enables the generation of naive iPSCs in a feeder-free culture. The naive iPSCs generated by this method show better differentiation to trilineage and extra-embryonic trophectoderm than those derived by conventional methods. This method can expand the application of iPSCs to research on early human development and regenerative medicine.

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