Evidence map›Paper›PMID 32434992›Full record

ArticleJCI insight2020

Persistent DNA damage-induced NLRP12 improves hematopoietic stem cell function.

Qiqi Lin, Limei Wu, Zhilin Ma, Fabliha Ahmed Chowdhury, Habibul Hasan Mazumder, Wei Du

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.9field-weighted citation impact, top 10% 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

11 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Reply to "The statistical significance may be misinterpreted".Journal of the Chinese Medical Association : JCMA · 2023
    Article
  6. Hematopoietic Stem Cells and the Immune System in Development and Aging.International journal of molecular sciences · 2023
    Review
  7. Review
  8. The landscape of aging.Science China. Life sciences · 2022
    Review
  9. DNA damage and repair in the hematopoietic system.Acta biochimica et biophysica Sinica · 2022
    Review
  10. Review
  11. 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

6 authors at 1 institution in 2 countries.

Qiqi LinDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia, USA.
Limei WuDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia, USA.
Zhilin MaDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia, USA.
Fabliha Ahmed ChowdhuryDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia, USA.
Habibul Hasan MazumderDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia, USA.
Wei DuDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia, USA.
West Virginia University · US

Funding

WVU Flow Cytometry and Single Cell Core Facility (FCSCCF)P20GM121322 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Dominique Bollino · 2018 to 2026
$22.4M
A novel immunometabolism-regulatory axis in inflammatory hematopoiesisR01HL151390 · NHLBI · WEST VIRGINIA UNIVERSITY · PI DU, WEI · 2020 to 2023
$1.5M
NHLBI NIH HHS R01 HL151390NIGMS NIH HHS P20 GM121322
6 · The paper itself

Abstract

NOD-like receptor 12 (NLRP12) is a member of the nucleotide-binding domain and leucine-rich repeat containing receptor inflammasome family that plays a central role in innate immunity. We previously showed that DNA damage upregulated NLRP12 in hematopoietic stem cells (HSCs) of mice deficient in the DNA repair gene Fanca. However, the role of NLRP12 in HSC maintenance is not known. Here, we show that persistent DNA damage-induced NLRP12 improves HSC function in both mouse and human models of DNA repair deficiency and aging. Specifically, treatment of Fanca-/- mice with the DNA cross-linker mitomycin C or ionizing radiation induces NLRP12 upregulation in phenotypic HSCs. NLRP12 expression is specifically induced by persistent DNA damage. Functionally, knockdown of NLRP12 exacerbates the repopulation defect of Fanca-/- HSCs. Persistent DNA damage-induced NLRP12 was also observed in the HSCs from aged mice, and depletion of NLRP12 in these aged HSCs compromised their self-renewal and hematopoietic recovery. Consistently, overexpression of NLRP12 substantially improved the long-term repopulating function of Fanca-/- and aged HSCs. Finally, persistent DNA damage-induced NLRP12 maintains the function of HSCs from patients with FA or aged donors. These results reveal a potentially novel role of NLRP12 in HSC maintenance and suggest that NLRP12 targeting has therapeutic potential in DNA repair disorders and aging.

Indexed as

DNA DamageHematopoiesisAgingAnimalsFanconi Anemia Complementation Group A ProteinHematopoietic Stem CellsIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutFanca protein, mouseFanconi Anemia Complementation Group A ProteinIntracellular Signaling Peptides and ProteinsNLRP12 protein, mouseAgingDNA repairHematologyHematopoietic stem cells

Identifiers

PMID32434992
PMCPMC7259522
OpenAlexW3026847684

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.