Generation of functional human oligodendrocytes from dermal fibroblasts by direct lineage conversion.
Direct lineage conversion
Fibroblasts
Human
Leukodystrophy
Myelination
Oligodendrocyte
Journal
Development (Cambridge, England)
ISSN: 1477-9129
Titre abrégé: Development
Pays: England
ID NLM: 8701744
Informations de publication
Date de publication:
15 10 2022
15 10 2022
Historique:
received:
21
04
2021
accepted:
03
05
2022
entrez:
24
6
2022
pubmed:
25
6
2022
medline:
28
6
2022
Statut:
ppublish
Résumé
Oligodendrocytes, the myelinating cells of the central nervous system, possess great potential for disease modeling and cell transplantation-based therapies for leukodystrophies. However, caveats to oligodendrocyte differentiation protocols ( Ehrlich et al., 2017; Wang et al., 2013; Douvaras and Fossati, 2015) from human embryonic stem and induced pluripotent stem cells (iPSCs), which include slow and inefficient differentiation, and tumorigenic potential of contaminating undifferentiated pluripotent cells, are major bottlenecks towards their translational utility. Here, we report the rapid generation of human oligodendrocytes by direct lineage conversion of human dermal fibroblasts (HDFs). We show that the combination of the four transcription factors OLIG2, SOX10, ASCL1 and NKX2.2 is sufficient to convert HDFs to induced oligodendrocyte precursor cells (iOPCs). iOPCs resemble human primary and iPSC-derived OPCs based on morphology and transcriptomic analysis. Importantly, iOPCs can differentiate into mature myelinating oligodendrocytes in vitro and in vivo. Finally, iOPCs derived from patients with Pelizaeus Merzbacher disease, a hypomyelinating leukodystrophy caused by mutations in the proteolipid protein 1 (PLP1) gene, showed increased cell death compared with iOPCs from healthy donors. Thus, human iOPCs generated by direct lineage conversion represent an attractive new source for human cell-based disease models and potentially myelinating cell grafts.
Identifiants
pubmed: 35748297
pii: 275808
doi: 10.1242/dev.199723
pmc: PMC9357374
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MC_PC_17230
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
© 2022. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
Références
Stem Cell Reports. 2019 Aug 13;13(2):254-261
pubmed: 31378671
Development. 2007 Jan;134(2):285-93
pubmed: 17166924
Development. 2002 Feb;129(3):681-93
pubmed: 11830569
Annu Rev Cell Dev Biol. 2014;30:503-33
pubmed: 25288117
Cell. 1983 Oct;34(3):799-806
pubmed: 6194889
J Neurosci. 2012 Oct 24;32(43):15012-26
pubmed: 23100423
Cell. 2012 Nov 21;151(5):994-1004
pubmed: 23159369
Nature. 2014 Apr 10;508(7495):199-206
pubmed: 24695229
Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):E2243-E2252
pubmed: 28246330
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
pubmed: 9843981
Cell Stem Cell. 2019 Oct 3;25(4):531-541.e6
pubmed: 31585094
Arch Pathol Lab Med. 2017 Feb;141(2):288-292
pubmed: 27628324
Stem Cell Reports. 2021 Apr 13;16(4):771-783
pubmed: 33770499
Cell Stem Cell. 2017 Aug 3;21(2):209-224.e7
pubmed: 28712938
Nat Biotechnol. 2013 May;31(5):426-33
pubmed: 23584611
J Neurosci. 2014 Sep 3;34(36):11929-47
pubmed: 25186741
Cell Stem Cell. 2015 Jan 8;16(1):39-50
pubmed: 25467916
Nat Biotechnol. 2011 Sep 25;29(10):934-41
pubmed: 21947029
Nat Neurosci. 2008 Nov;11(11):1271-82
pubmed: 18849986
Nat Commun. 2014 Jun 17;5:4112
pubmed: 24934763
Neuroscience. 2013 Dec 3;253:256-73
pubmed: 23999125
Mol Psychiatry. 2016 Jan;21(1):62-70
pubmed: 26216300
Expert Rev Mol Med. 2008 May 19;10:e14
pubmed: 18485258
Stem Cell Reports. 2014 Apr 24;2(5):648-61
pubmed: 24936452
Curr Opin Cell Biol. 2005 Dec;17(6):639-47
pubmed: 16226447
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2948-53
pubmed: 11867759
Cell Stem Cell. 2013 Feb 7;12(2):252-64
pubmed: 23395447
Bioinformatics. 2004 Nov 22;20(17):3246-8
pubmed: 15180930
Nature. 2009 Aug 27;460(7259):1132-5
pubmed: 19668191
Adv Neurobiol. 2017;15:211-252
pubmed: 28674983
Nature. 2009 Dec 3;462(7273):595-601
pubmed: 19898493
Nature. 2014 Nov 13;515(7526):264-8
pubmed: 25391964
Nat Neurosci. 2018 Sep;21(9):1171-1184
pubmed: 30154505
Development. 2014 Oct;141(19):3721-31
pubmed: 25249462
Sci Transl Med. 2012 Oct 10;4(155):155ra137
pubmed: 23052294
Nat Protoc. 2015 Aug;10(8):1143-54
pubmed: 26134954
Nat Biotechnol. 2013 May;31(5):434-9
pubmed: 23584610
Genes Dev. 1996 Apr 1;10(7):826-35
pubmed: 8846919
Cell. 2007 Nov 30;131(5):861-72
pubmed: 18035408
J Neurosci. 2014 Feb 5;34(6):2169-90
pubmed: 24501358
Development. 2014 Jun;141(11):2216-24
pubmed: 24821983
Development. 2008 Apr;135(7):1271-81
pubmed: 18287202
Sci Transl Med. 2012 Oct 10;4(155):155ra136
pubmed: 23052293
Genes Dev. 2011 May 1;25(9):930-45
pubmed: 21536733
J Neurosci. 2007 Apr 18;27(16):4233-42
pubmed: 17442807
Nat Neurosci. 2008 Aug;11(8):888-93
pubmed: 18587391
Nat Methods. 2018 Sep;15(9):700-706
pubmed: 30046099
Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12759-64
pubmed: 19549847
Nat Commun. 2015 Dec 07;6:10100
pubmed: 26639555
Cell. 2015 Apr 23;161(3):555-568
pubmed: 25892221