Evidence map›Paper›PMID 32727902›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Lsh/HELLS is required for B lymphocyte development and immunoglobulin class switch recombination.

Yafeng He, Jianke Ren, Xiaoping Xu, Kai Ni, Andrew Schwader, Richard Finney, Can Wang, Lei Sun, Kimberly Klarmann, Jonathan Keller and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

25 citing papers in PubMed, 30 citations in OpenAlex.

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  14. The aberrant epigenome ofGenome research · 2023
    Article
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  17. Epidemiology of Δ8THC-Related Carcinogenesis in USA: A Panel Regression and Causal Inferential Study.International journal of environmental research and public health · 2022
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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

13 authors at 2 institutions in 1 country.

Yafeng HeEpigenetics Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Jianke RenEpigenetics Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Xiaoping XuEpigenetics Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Kai NiEpigenetics Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Andrew SchwaderEpigenetics Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Richard FinneyCCR Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
Can WangEpigenetics Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Lei SunHematopoiesis and Stem Cell Biology Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Kimberly KlarmannHematopoiesis and Stem Cell Biology Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Jonathan KellerHematopoiesis and Stem Cell Biology Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Anthony TubbsLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892.
Andre NussenzweigLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892.
Kathrin MueggeEpigenetics Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702; Kathrin.Muegge@nih.gov.ORCID 0000-0003-1396-4282
National Cancer Institute · USLeidos (United States) · US

Funding

Epigenetic control during embryogenesisZIABC010014 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MUEGGE, KATHRIN · 2009 to 2025
$18.1M
6 · The paper itself

Abstract

Mutation of HELLS (Helicase, Lymphoid-Specific)/Lsh in human DNA causes a severe immunodeficiency syndrome, but the nature of the defect remains unknown. We assessed here the role of Lsh in hematopoiesis using conditional Lsh knockout mice with expression of Mx1 or Vav Cre-recombinase. Bone marrow transplantation studies revealed that Lsh depletion in hematopoietic stem cells severely reduced B cell numbers and impaired B cell development in a hematopoietic cell-autonomous manner. Lsh-deficient mice without bone marrow transplantation exhibited lower Ig levels in vivo compared to controls despite normal peripheral B cell numbers. Purified B lymphocytes proliferated normally but produced less immunoglobulins in response to in vitro stimulation, indicating a reduced capacity to undergo class switch recombination (CSR). Analysis of germline transcripts, examination of double-stranded breaks using biotin-labeling DNA break assay, and End-seq analysis indicated that the initiation of the recombination process was unscathed. In contrast, digestion-circularization PCR analysis and high-throughput sequencing analyses of CSR junctions and a chromosomal break repair assay indicated an impaired ability of the canonical end-joining pathway in Lsh-deficient B cells. Our data suggest a hematopoietic cell-intrinsic role of Lsh in B cell development and in CSR providing a potential target for immunodeficiency therapy.

Indexed as

AnimalsB-LymphocytesCell LineDNA HelicasesGene SilencingHumansImmunoglobulinsMiceMice, KnockoutMutationDNA HelicasesHELLS protein, humanImmunoglobulinslymphoid specific helicase, mousechromatin remodelerclass switch recombinationICF syndromeLsh

Identifiers

PMID32727902
PMCPMC7443918
OpenAlexW3045803804

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.