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Transcription factor-based direct conversion of human fibroblasts to functional astrocytes

Quist, Ella LU orcid ; Trovato, Francesco LU ; Avaliani, Natalia LU ; Zetterdahl, Oskar G. LU ; Gonzalez-Ramos, Ana LU ; Hansen, Marita G. LU ; Kokaia, Merab LU ; Canals, Isaac LU and Ahlenius, Henrik LU (2022) In Stem Cell Reports 17(7). p.1620-1635
Abstract

Astrocytes are emerging key players in neurological disorders. However, their role in disease etiology is poorly understood owing to inaccessibility of primary human astrocytes. Pluripotent stem cell-derived cells fail to mimic age and due to their clonal origin do not mimic genetic heterogeneity of patients. In contrast, direct conversion constitutes an attractive approach to generate human astrocytes that capture age and genetic diversity. We describe efficient direct conversion of human fibroblasts to functional induced astrocytes (iAs). Expression of the minimal combination Sox9 and Nfib generates iAs with molecular, phenotypic, and functional properties resembling primary human astrocytes. iAs could be obtained by conversion of... (More)

Astrocytes are emerging key players in neurological disorders. However, their role in disease etiology is poorly understood owing to inaccessibility of primary human astrocytes. Pluripotent stem cell-derived cells fail to mimic age and due to their clonal origin do not mimic genetic heterogeneity of patients. In contrast, direct conversion constitutes an attractive approach to generate human astrocytes that capture age and genetic diversity. We describe efficient direct conversion of human fibroblasts to functional induced astrocytes (iAs). Expression of the minimal combination Sox9 and Nfib generates iAs with molecular, phenotypic, and functional properties resembling primary human astrocytes. iAs could be obtained by conversion of fibroblasts covering the entire human lifespan. Importantly, iAs supported function of induced neurons obtained through direct conversion from the same fibroblast population. Fibroblast-derived iAs will become a useful tool to elucidate the biology of astrocytes and complement current in vitro models for studies of late-onset neurological disorders.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
astrocytes, direct conversion, fibroblasts, neurodegenerative diseases, neurons, Nfia, Nfib, Sox9, transcription factors, transdifferentiation
in
Stem Cell Reports
volume
17
issue
7
pages
16 pages
publisher
Cell Press
external identifiers
  • pmid:35750047
  • scopus:85133691316
ISSN
2213-6711
DOI
10.1016/j.stemcr.2022.05.015
language
English
LU publication?
yes
id
7fd99df6-7267-443c-8108-01aa14181d49
date added to LUP
2022-09-23 15:37:56
date last changed
2024-04-15 19:12:28
@article{7fd99df6-7267-443c-8108-01aa14181d49,
  abstract     = {{<p>Astrocytes are emerging key players in neurological disorders. However, their role in disease etiology is poorly understood owing to inaccessibility of primary human astrocytes. Pluripotent stem cell-derived cells fail to mimic age and due to their clonal origin do not mimic genetic heterogeneity of patients. In contrast, direct conversion constitutes an attractive approach to generate human astrocytes that capture age and genetic diversity. We describe efficient direct conversion of human fibroblasts to functional induced astrocytes (iAs). Expression of the minimal combination Sox9 and Nfib generates iAs with molecular, phenotypic, and functional properties resembling primary human astrocytes. iAs could be obtained by conversion of fibroblasts covering the entire human lifespan. Importantly, iAs supported function of induced neurons obtained through direct conversion from the same fibroblast population. Fibroblast-derived iAs will become a useful tool to elucidate the biology of astrocytes and complement current in vitro models for studies of late-onset neurological disorders.</p>}},
  author       = {{Quist, Ella and Trovato, Francesco and Avaliani, Natalia and Zetterdahl, Oskar G. and Gonzalez-Ramos, Ana and Hansen, Marita G. and Kokaia, Merab and Canals, Isaac and Ahlenius, Henrik}},
  issn         = {{2213-6711}},
  keywords     = {{astrocytes; direct conversion; fibroblasts; neurodegenerative diseases; neurons; Nfia; Nfib; Sox9; transcription factors; transdifferentiation}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{1620--1635}},
  publisher    = {{Cell Press}},
  series       = {{Stem Cell Reports}},
  title        = {{Transcription factor-based direct conversion of human fibroblasts to functional astrocytes}},
  url          = {{http://dx.doi.org/10.1016/j.stemcr.2022.05.015}},
  doi          = {{10.1016/j.stemcr.2022.05.015}},
  volume       = {{17}},
  year         = {{2022}},
}