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Record W3138750498 · doi:10.1016/j.stemcr.2021.03.001

One-step Reprogramming of Human Fibroblasts into Oligodendrocyte-like Cells by SOX10, OLIG2, and NKX6.2

2021· article· en· W3138750498 on OpenAlexaff
Konstantina Chanoumidou, Benjamín Hernández-Rodríguez, Farina Windener, Christian Thomas, Martin Stehling, Sabah Mozafari, Stefanie Albrecht, Linda Ottoboni, Jack P. Antel, Kee-Pyo Kim, Sergiy Velychko, Qiao Ling Cui, Yu Kang T. Xu, Gianvito Martino, Jürgen Winkler, Hans R. Schöler, Anne Baron‐Van Evercooren, Odile Boespflug‐Tanguy, Juan M. Vaquerizas, Marc Ehrlich, Tanja Kuhlmann

Bibliographic record

VenueStem Cell Reports · 2021
Typearticle
Languageen
FieldNeuroscience
TopicNeurogenesis and neuroplasticity mechanisms
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersSeventh Framework ProgrammeMedical Research CouncilMax-Planck-GesellschaftDeutsche ForschungsgemeinschaftInterdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum WürzburgFrench Muscular Dystrophy AssociationAgence Nationale de la RechercheHorizon 2020NovartisNational Multiple Sclerosis Society
KeywordsOLIG2BiologySOX10RemyelinationOligodendrocyteReprogrammingCell biologyMyelinDNA methylationCancer researchNeuroscienceGeneticsGene expressionCellGeneCentral nervous systemEmbryo

Abstract

fetched live from OpenAlex

Limited access to human oligodendrocytes impairs better understanding of oligodendrocyte pathology in myelin diseases. Here, we describe a method to robustly convert human fibroblasts directly into oligodendrocyte-like cells (dc-hiOLs), which allows evaluation of remyelination-promoting compounds and disease modeling. Ectopic expression of SOX10, OLIG2, and NKX6.2 in human fibroblasts results in rapid generation of O4 + cells, which further differentiate into MBP + mature oligodendrocyte-like cells within 16 days. dc-hiOLs undergo chromatin remodeling to express oligodendrocyte markers, ensheath axons, and nanofibers in vitro , respond to promyelination compound treatment, and recapitulate in vitro oligodendroglial pathologies associated with Pelizaeus-Merzbacher leukodystrophy related to PLP1 mutations. Furthermore, DNA methylome analysis provides evidence that the CpG methylation pattern significantly differs between dc-hiOLs derived from fibroblasts of young and old donors, indicating the maintenance of the source cells' "age." In summary, dc-hiOLs represent a reproducible technology that could contribute to personalized medicine in the field of myelin diseases.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.021
GPT teacher head0.240
Teacher spread0.219 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations39
Published2021
Admission routes1
Has abstractyes

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