Improved Sendai viral system for reprogramming to naive pluripotency

Cell Rep Methods. 2022 Oct 17;2(11):100317. doi: 10.1016/j.crmeth.2022.100317. eCollection 2022 Nov 21.

Abstract

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.

Keywords: LMYC; Sendai virus vector; extra-embryonic trophectoderm; feeder-free culture; hsa-microRNA-367; induced pluripotent stem cells; naive pluripotency; reprogramming; residual transgenes; temperature sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Differentiation / genetics
  • Cellular Reprogramming / genetics
  • Genetic Vectors
  • Humans
  • Induced Pluripotent Stem Cells*
  • Sendai virus / genetics