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  Donor cell memory confers a metastable state of directly converted cells

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.

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 Creators:
Kim, Kee-Pyo, Author
Li, Cui, Author
Bunina, Daria, Author
Jeong, Hyun-Woo, Author
Ghelman, Julia, Author
Yoon, Juyong, Author
Shin, Borami, Author
Park, Hongryeol, Author
Han, Dong Wook, Author
Zaugg, Judith B., Author
Kim, Johnny1, Author              
Kuhlmann, Tanja, Author
Adams, Ralf H., Author
Noh, Kyung-Min, Author
Goldman, Steven A., Author
Schoeler, Hans R., Author
Affiliations:
1Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              

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Free keywords: PROGENITOR CELLS; MOUSE; MYELINATION; STEM; PERICYTES; SHIVERER; SYSTEM; CNS; OLIGODENDROCYTES; DIFFERENTIATIONCell Biology;
 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.

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Language(s): eng - English
 Dates: 2021-04-122021-07-01
 Publication Status: Published in print
 Pages: 26
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000669345800011
DOI: 10.1016/j.stem.2021.02.023
PMID: 33848472
 Degree: -

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Title: CELL STEM CELL
Source Genre: Journal
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Publ. Info: 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 28 (7) Sequence Number: - Start / End Page: 1291 - 1306 Identifier: ISSN: 1934-5909