Evidence map›Paper›PMID 31099332›Full record

ArticleeLife2019

Chemical modulation of transcriptionally enriched signaling pathways to optimize the conversion of fibroblasts into neurons.

Joseph Herdy, Simon Schafer, Yongsung Kim, Zoya Ansari, Dina Zangwill, Manching Ku, Apua Paquola, Hyungjun Lee, Jerome Mertens, Fred H Gage

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

43 citing papers in PubMed, 61 citations in OpenAlex.

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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

10 authors at 3 institutions in 3 countries.

Joseph HerdyLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, United States.ORCID http://orcid.org/0000-0002-8636-8134
Simon SchaferLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, United States.
Yongsung KimLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, United States.
Zoya AnsariLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, United States.
Dina ZangwillLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, United States.
Manching KuUniversity Hospital Freiberg, University of Freiberg, Breisgau, Germany.ORCID http://orcid.org/0000-0001-5168-4308
Apua PaquolaLieber Institute for Brain Development, Baltimore, United States.
Hyungjun LeeLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, United States.
Jerome MertensLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, United States.
Fred H GageLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, United States.ORCID http://orcid.org/0000-0002-0938-4106
Salk Institute for Biological Studies · USLieber Institute for Brain Development · USTU Bergakademie Freiberg · DE

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8M
Research Training in BiogerontologyT32AG000114 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCOTT PLETCHER · 1985 to 2026
$12.4M
Assessing cellular aging in old and rejuvenated neurons from Alzheimer patientsR01AG056306 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI GAGE, FRED H · 2017 to 2021
$2.4M
Assessing cellular aging in old and rejuvenated neurons from Alzheimer patientsK99AG056679 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI MERTENS, JEROME S. · 2017 to 2018
$201k
NCI NIH HHS P30 CA014195NIA NIH HHS K99 AG056679NIA NIH HHS K99-AG056679-01NIA NIH HHS R01 AG056306NIA NIH HHS R01-AG056306-01NIA NIH HHS T32 AG000114
6 · The paper itself

Abstract

Direct conversion of human somatic fibroblasts into induced neurons (iNs) allows for the generation of functional neurons while bypassing any stem cell intermediary stages. Although iN technology has an enormous potential for modeling age-related diseases, as well as therapeutic approaches, the technology faces limitations due to variable conversion efficiencies and a lack of thorough understanding of the signaling pathways directing iN conversion. Here, we introduce a new all-in-one inducible lentiviral system that simplifies fibroblast transgenesis for the two pioneer transcription factors, Ngn2 and Ascl1, and markedly improves iN yields. Further, our timeline RNA-Seq data across the course of conversion has identified signaling pathways that become transcriptionally enriched during iN conversion. Small molecular modulators were identified for four signaling pathways that reliably increase the yield of iNs. Taken together, these advances provide an improved toolkit for iN technology and new insight into the mechanisms influencing direct iN conversion.

Indexed as

Cell TransdifferentiationAdolescentAdultAgedAged, 80 and overBasic Helix-Loop-Helix ProteinsCells, CulturedChildChild, PreschoolFibroblastsGene Expression ProfilingGene Transfer TechniquesHumansInfantInfant, NewbornMiddle AgedASCL1 protein, humanBasic Helix-Loop-Helix ProteinsNerve Tissue ProteinsNEUROG2 protein, humandirect reprogramminghumaniNinduced neuronslentiviruspathway analysisregenerative medicinestem cellstransgenesis

Identifiers

PMID31099332
PMCPMC6524968
OpenAlexW2946301480

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.