Direct lineage conversion of adult mouse liver cells and B lymphocytes to neural stem cells

Research output: Contribution to journalArticlepeer-review

Authors

  • John P Cassady
  • Ana C D'Alessio
  • Vardhan S Dani
  • Zi Peng Fan
  • Kibibi Ganz
  • Reinhard Roessler
  • Mriganka Sur
  • Richard A Young
  • Rudolf Jaenisch

Colleges, School and Institutes

Abstract

Overexpression of transcription factors has been used to directly reprogram somatic cells into a range of other differentiated cell types, including multipotent neural stem cells (NSCs), that can be used to generate neurons and glia. However, the ability to maintain the NSC state independent of the inducing factors and the identity of the somatic donor cells remain two important unresolved issues in transdifferentiation. Here we used transduction of doxycycline-inducible transcription factors to generate stable tripotent NSCs. The induced NSCs (iNSCs) maintained their characteristics in the absence of exogenous factor expression and were transcriptionally, epigenetically, and functionally similar to primary brain-derived NSCs. Importantly, we also generated tripotent iNSCs from multiple adult cell types, including mature liver and B cells. Our results show that self-maintaining proliferative neural cells can be induced from nonectodermal cells by expressing specific combinations of transcription factors.

Details

Original languageEnglish
Pages (from-to)948-56
Number of pages9
JournalStem Cell Reports
Volume3
Issue number6
Early online date6 Nov 2014
Publication statusPublished - 9 Dec 2014

Keywords

  • Animals, B-Lymphocytes, Cell Lineage, Cell Transdifferentiation, Cellular Reprogramming, Cluster Analysis, Epigenesis, Genetic, Gene Expression, Gene Expression Profiling, Hepatocytes, Mice, Neural Stem Cells, Transcription Factors, Transcription, Genetic