Evidence map›Paper›PMID 29517978›Full record

ArticleThe Journal of clinical investigation2018

TRAP-seq identifies cystine/glutamate antiporter as a driver of recovery from liver injury.

Amber W Wang, Kirk J Wangensteen, Yue J Wang, Adam M Zahm, Nicholas G Moss, Noam Erez, Klaus H Kaestner

Open access · greenAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.9field-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

20 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Distinct hepatocyte identities in liver homeostasis and regeneration.JHEP reports : innovation in hepatology · 2023
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Inhibiting xCT/SLC7A11 induces ferroptosis of myofibroblastic hepatic stellate cells but exacerbates chronic liver injury.Liver international : official journal of the International Association for the Study of the Liver · 2021
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. The Dynamic Chromatin Architecture of the Regenerating Liver.Cellular and molecular gastroenterology and hepatology · 2020
    Article
  16. Cell Type-specific Gene Expression Profiling in the Mouse Liver.Journal of visualized experiments : JoVE · 2019
    Article
  17. Review
  18. Article
  19. Article
  20. Prometheus revisited.The Journal of clinical investigation · 2018
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Amber W WangDepartment of Genetics and.
Kirk J WangensteenDepartment of Genetics and.
Yue J WangDepartment of Genetics and.
Adam M ZahmDepartment of Genetics and.
Nicholas G MossDepartment of Genetics and.
Noam ErezDepartment of Genetics and.
Klaus H KaestnerDepartment of Genetics and.
University of Pennsylvania · US

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI DOUGLAS J EPSTEIN · 1986 to 2026
$48.3M
TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GARY D. WU · 1997 to 2026
$32.5M
PREDOCTORAL TRAINING PROGRAM IN PHARMACOLOGYT32GM008076 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BLENDY, JULIE A · 1985 to 2023
$10.8M
Innovative Genetic Approaches for Hepatic RepopulationR01DK102667 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KAESTNER, KLAUS H · 2015 to 2019
$1.8M
Genetic basis of liver repopulationK08DK106478 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI WANGENSTEEN, KIRK J · 2015 to 2019
$787k
Role of microRNAs in pediatric inflammatory bowel diseaseK01DK102868 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI ZAHM, ADAM MATTHEW · 2015 to 2019
$665k
Elucidating Redox Regulation in the Repopulating LiverF31DK113666 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI WANG, AMBER WEICHING · 2017 to 2019
$94k
NIDDK NIH HHS F31 DK113666NIDDK NIH HHS K01 DK102868NIDDK NIH HHS K08 DK106478NIDDK NIH HHS P30 DK019525NIDDK NIH HHS P30 DK050306NIDDK NIH HHS R01 DK102667NIGMS NIH HHS T32 GM008076
6 · The paper itself

Abstract

Understanding the molecular basis of the regenerative response following hepatic injury holds promise for improved treatment of liver diseases. Here, we report an innovative method to profile gene expression specifically in the hepatocytes that regenerate the liver following toxic injury. We used the Fah-/- mouse, a model of hereditary tyrosinemia, which conditionally undergoes severe liver injury unless fumarylacetoacetate hydrolase (FAH) expression is reconstituted ectopically. We used translating ribosome affinity purification followed by high-throughput RNA sequencing (TRAP-seq) to isolate mRNAs specific to repopulating hepatocytes. We uncovered upstream regulators and important signaling pathways that are highly enriched in genes changed in regenerating hepatocytes. Specifically, we found that glutathione metabolism, particularly the gene Slc7a11 encoding the cystine/glutamate antiporter (xCT), is massively upregulated during liver regeneration. Furthermore, we show that Slc7a11 overexpression in hepatocytes enhances, and its suppression inhibits, repopulation following toxic injury. TRAP-seq allows cell type-specific expression profiling in repopulating hepatocytes and identified xCT, a factor that supports antioxidant responses during liver regeneration. xCT has potential as a therapeutic target for enhancing liver regeneration in response to liver injury.

Indexed as

LiverLiver RegenerationAmino Acid Transport System y+AnimalsHepatocytesMiceMice, KnockoutTyrosinemiasAmino Acid Transport System y+Slc7a11 protein, mouseExpression profilingGastroenterologyHepatologyMolecular geneticsMouse models

Identifiers

PMID29517978
PMCPMC5983312
OpenAlexW2794216885

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.