Donor cell memory confers a metastable state of directly converted cells

Research output: Contribution to journalJournal articleResearchpeer-review

  • Kee Pyo Kim
  • Cui Li
  • Daria Bunina
  • Hyun Woo Jeong
  • Julia Ghelman
  • Juyong Yoon
  • Borami Shin
  • Hongryeol Park
  • Dong Wook Han
  • Judith B. Zaugg
  • Johnny Kim
  • Tanja Kuhlmann
  • Ralf H. Adams
  • Kyung Min Noh
  • Goldman, Steven Alan
  • Hans R. Schöler

Generation of induced oligodendrocyte progenitor cells (iOPCs) from somatic fibroblasts is a strategy for cell-based therapy of myelin diseases. However, iOPC generation is inefficient, and the resulting iOPCs exhibit limited expansion and differentiation competence. Here we overcome these limitations by transducing an optimized transcription factor combination into a permissive donor phenotype, the pericyte. Pericyte-derived iOPCs (PC-iOPCs) are stably expandable and functionally myelinogenic with high differentiation competence. Unexpectedly, however, we found that PC-iOPCs are metastable so that they can produce myelination-competent oligodendrocytes or revert to their original identity in a context-dependent fashion. Phenotypic reversion of PC-iOPCs is tightly linked to memory of their original transcriptome and epigenome. Phenotypic reversion can be disconnected from this donor cell memory effect, and in vivo myelination can eventually be achieved by transplantation of O4+ pre-oligodendrocytes. Our data show that donor cell source and memory can contribute to the fate and stability of directly converted cells.

Original languageEnglish
JournalCell Stem Cell
Volume28
Issue number7
Pages (from-to)1291-1306.e10
Number of pages17
ISSN1934-5909
DOIs
Publication statusPublished - 2021

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Inc.

    Research areas

  • direct conversion, donor cell memory, iOPCs, metastable, OLIG2, oligodendrocyte progenitor cells, oligodendrocytes, pericytes, reprogramming, SOX10

ID: 371930933