English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Donor cell memory confers a metastable state of directly converted cells

MPS-Authors
/persons/resource/persons224132

Kim,  Johnny
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Kim, K.-P., Li, C., Bunina, D., Jeong, H.-W., Ghelman, J., Yoon, J., et al. (2021). Donor cell memory confers a metastable state of directly converted cells. CELL STEM CELL, 28(7), 1291-1306. doi:10.1016/j.stem.2021.02.023.


Cite as: https://hdl.handle.net/21.11116/0000-0008-F839-1
Abstract
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.