Evidence map›Paper›PMID 37126716›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

Direct neuronal reprogramming by temporal identity factors.

Camille Boudreau-Pinsonneault, Luke Ajay David, José Alex Lourenço Fernandes, Awais Javed, Michel Fries, Pierre Mattar, Michel Cayouette

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
6.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
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  9. The neuroimmune interface in retinal regeneration.Progress in retinal and eye research · 2025
    Review
  10. Article
  11. Timing neural development and regeneration.Current opinion in neurobiology · 2025
    Review
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  13. Article
  14. Article
  15. Article
  16. Article
  17. IKAROS Family Transcription Factors in Lymphocyte Differentiation and Function.Advances in experimental medicine and biology · 2024
    Review
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Camille Boudreau-PinsonneaultCellular Neurobiology Research Unit, Montreal Clinical Research Institute (IRCM), Montreal, QC H2W 1R7, Canada.
Luke Ajay DavidCellular Neurobiology Research Unit, Montreal Clinical Research Institute (IRCM), Montreal, QC H2W 1R7, Canada.ORCID 0000-0003-4613-8032
José Alex Lourenço FernandesOttawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.ORCID 0000-0003-2995-5452
Awais JavedCellular Neurobiology Research Unit, Montreal Clinical Research Institute (IRCM), Montreal, QC H2W 1R7, Canada.
Michel FriesCellular Neurobiology Research Unit, Montreal Clinical Research Institute (IRCM), Montreal, QC H2W 1R7, Canada.
Pierre MattarOttawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.ORCID 0000-0002-5708-6218
Michel CayouetteCellular Neurobiology Research Unit, Montreal Clinical Research Institute (IRCM), Montreal, QC H2W 1R7, Canada.ORCID 0000-0003-4655-9048
Montreal Clinical Research Institute · CAUniversity of Ottawa · CA

Funding

CIHR FDN-159936CIHR PJT-166032CIHR PJT-166074
6 · The paper itself

Abstract

Temporal identity factors are sufficient to reprogram developmental competence of neural progenitors and shift cell fate output, but whether they can also reprogram the identity of terminally differentiated cells is unknown. To address this question, we designed a conditional gene expression system that allows rapid screening of potential reprogramming factors in mouse retinal glial cells combined with genetic lineage tracing. Using this assay, we found that coexpression of the early temporal identity transcription factors Ikzf1 and Ikzf4 is sufficient to directly convert Müller glial (MG) cells into cells that translocate to the outer nuclear layer (ONL), where photoreceptor cells normally reside. We name these "induced ONL (iONL)" cells. Using genetic lineage tracing, histological, immunohistochemical, and single-cell transcriptome and multiome analyses, we show that expression of Ikzf1/4 in MG in vivo, without retinal injury, mostly generates iONL cells that share molecular characteristics with bipolar cells, although a fraction of them stain for Rxrg, a cone photoreceptor marker. Furthermore, we show that coexpression of Ikzf1 and Ikzf4 can reprogram mouse embryonic fibroblasts to induced neurons in culture by rapidly remodeling chromatin and activating a neuronal gene expression program. This work uncovers general neuronal reprogramming properties for temporal identity factors in terminally differentiated cells.

Indexed as

FibroblastsRetinaAnimalsCell DifferentiationCellular ReprogrammingMiceRetinal Cone Photoreceptor CellsTranscription FactorsTranscription Factorscell therapyregenerationreprogrammingretinatranscription factors

Identifiers

PMID37126716
PMCPMC10175841
OpenAlexW4367625696

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.