Evidence map›Paper›PMID 22869756›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Reprogramming IgH isotype-switched B cells to functional-grade induced pluripotent stem cells.

Duane R Wesemann, Andrew J Portuguese, Jennifer M Magee, Michael P Gallagher, Xiaolong Zhou, Rohit A Panchakshari, Frederick W Alt

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

13 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. IgE Glycosylation in Health and Disease.Current topics in microbiology and immunology · 2019
    Review
  5. Review
  6. IgH isotype-specific B cell receptor expression influences B cell fate.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  7. Article
  8. Article
  9. Detection of true IgE-expressing mouse B lineage cells.Journal of visualized experiments : JoVE · 2014
    Article
  10. DLK1-DIO3 imprinted cluster in induced pluripotency: landscape in the mist.Cellular and molecular life sciences : CMLS · 2014
    Review
  11. Lymphocyte-based model systems for allergy research: a historic overview.International archives of allergy and immunology · 2014
    Review
  12. Article
  13. Article
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 3 institutions in 1 country.

Duane R WesemannProgram in Cellular and Molecular Medicine and Immune Disease Institute, Boston Children's Hospital, Boston, MA 02115, USA. wesemann@idi.harvard.edu
Andrew J Portuguese
Jennifer M Magee
Michael P Gallagher
Xiaolong Zhou
Rohit A Panchakshari
Frederick W Alt
Howard Hughes Medical Institute · USBoston Children's Hospital · USHarvard University · US

Funding

Mechanisms that Control IgH Variable Region Exon AssemblyR01AI020047 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI ALT, FREDERICK W. · 1985 to 2025
$14.1M
Molecular Mechanisms of Class Switch RecombinationR01AI077595 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI ALT, FREDERICK W. · 2009 to 2018
$4.3M
Peripheral B Cell Receptor EditingK08AI089972 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI WESEMANN, DUANE R. · 2010 to 2014
$685k
ASSEMBLY AND EXPRESSION OF IG VARIBLE REGION GENESR37AI020047 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI ALT, FREDERICK W · 1991 to 2000
$323k
Howard Hughes Medical InstituteNIAID NIH HHS AI020047NIAID NIH HHS AI077595NIAID NIH HHS K08 AI089972NIAID NIH HHS K08AI89972NIAID NIH HHS R01 AI020047NIAID NIH HHS R01 AI077595NIAID NIH HHS R37 AI020047
6 · The paper itself

Abstract

Induced pluripotent stem cells (iPSCs) can be formed from somatic cells by a defined set of genetic factors; however, aberrant epigenetic silencing of the imprinted Dlk1-Dio3 gene cluster often hinders their developmental potency and ability to contribute to high-grade chimerism in mice. Here, we describe an approach that allows splenic B cells activated to undergo Ig heavy-chain (IgH) class-switch recombination (CSR) to be reprogrammed into iPSCs that contribute to high-grade chimerism in mice. Treatment of naïve splenic B cells in culture with anti-CD40 plus IL-4 induces IgH CSR from IgM to IgG1 and IgE. CSR leads to irreversible IgH locus deletions wherein the IgM-producing Cμ exons are permanently excised from the B-cell genome. We find that anti-CD40 plus IL-4-activated B cells produce iPSCs that are uniformly hypermethylated in the imprinted Dlk1-Dio3 gene cluster and fail to produce chimerism in mice. However, treatment of activated B cells with the methyltransferase inhibitor 5-aza-2'-deoxycytidine before and at early stages of reprogramming attenuates hypermethylation of the Dlk1-Dio3 locus in resultant iPSCs and enables them to form high-grade chimerism in mice. These conditions allowed us to produce chimeric mice in which all mature B cells were derived entirely from IgG1-expressing B-cell-derived iPSCs. We conclude that culture conditions of activated B cells before and at early stages of reprogramming influence the developmental potency of resultant iPSCs.

Indexed as

AnimalsB-LymphocytesCell SeparationCytological TechniquesDNA-Binding ProteinsFlow CytometryGenetic TechniquesGenomeImmunoglobulin Class SwitchingImmunoglobulin Heavy ChainsInduced Pluripotent Stem CellsMiceMice, Inbred C57BLMice, TransgenicMultigene FamilyPluripotent Stem CellsDNA-Binding ProteinsImmunoglobulin Heavy ChainsRag2 protein, mouse

Identifiers

PMID22869756
PMCPMC3427115
OpenAlexW2019047745

What OpenQuestion holds

Textmetadata
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.