Evidence map›Paper›PMID 37832542›Full record

ArticleStem cell reports2023

Synthetic augmentation of bilirubin metabolism in human pluripotent stem cell-derived liver organoids.

Hasan Al Reza, Zishaan Farooqui, Abid Al Reza, Callen Conroy, Kentaro Iwasawa, Yasuhiro Ogura, Keisuke Okita, Kenji Osafune, Takanori Takebe

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

7 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Organoids for Metabolic Disease Modeling.Journal of inherited metabolic disease · 2026
    Review
  3. Article
  4. Article
  5. Article
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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

9 authors at 5 institutions in 2 countries.

Hasan Al RezaDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Zishaan FarooquiDivision of Gastroenterology, Hepatology & Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Abid Al RezaDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Callen ConroyCollege of Medicine, University of Kentucky, Lexington, KY, USA.
Kentaro IwasawaDivision of Gastroenterology, Hepatology & Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Yasuhiro OguraDepartment of Transplantation Surgery, Nagoya University Hospital, Nagoya University Graduate School of Medicine, Aichi, Japan.
Keisuke OkitaCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Kenji OsafuneCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Takanori TakebeDivision of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Gastroenterology, Hepatology & Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Institute of Research, Tokyo Medical and Dental University, Tokyo, Japan; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), and Division of Stem Cell and Organoid Medicine, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: takanori.takebe@cchmc.org.
Cincinnati Children's Hospital Medical Center · USKyoto University · JPNagoya University Hospital · JPTokyo Medical and Dental University · JPUniversity of Kentucky · US

Funding

Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Theresa Alenghat · 2007 to 2026
$24.4M
Modeling diabetes using an integrated plate systemUH3DK119982 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI LEE, MOO-YEAL, WELLS, JAMES M · 2020 to 2022
$5.4M
Engineering multi-organs in a dishDP2DK128799 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI TAKEBE, TAKANORI · 2020 to 2020
$2.3M
Modeling diabetes using an integrated plate systemUG3DK119982 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI LEE, MOO-YEAL, WELLS, JAMES M · 2018 to 2019
$1.7M
Organoid-guided Precision Hepatology for SteatohepatitisR01DK135478 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Takanori Takebe · 2024 to 2026
$1.6M
NIDDK NIH HHS DP2 DK128799NIDDK NIH HHS P30 DK078392NIDDK NIH HHS R01 DK135478NIDDK NIH HHS UG3 DK119982NIDDK NIH HHS UH3 DK119982
6 · The paper itself

Abstract

UGT1A1 (UDP glucuronosyltransferase family 1 member A1) is the primary enzyme required for bilirubin conjugation, which is essential for preventing hyperbilirubinemia. Animal models lack key human organic anion transporting polypeptides with distinct epigenetic control over bilirubin metabolism, necessitating a human model to interrogate the regulatory mechanism behind UGT1A1 function. Here, we use induced pluripotent stem cells to develop human liver organoids that can emulate conjugation failure phenotype. Bilirubin conjugation assays, chromatin immunoprecipitation, and transcriptome analysis elucidated the role of glucocorticoid antagonism in UGT1A1 activation. This antagonism prevents the binding of transcriptional repressor MECP2 at the expense of NRF2 with associated off-target effects. Therefore, we introduced functional GULO (L-gulonolactone oxidase) in human organoids to augment intracellular ascorbate for NRF2 reactivation. This engineered organoid conjugated more bilirubin and protected against hyperbilirubinemia when transplanted in immunosuppressed Crigler-Najjar syndrome rat model. Collectively, we demonstrate that our organoid system serves as a manipulatable model for interrogating hyperbilirubinemia and potential therapeutic development.

Indexed as

Crigler-Najjar SyndromePluripotent Stem CellsAnimalsBilirubinGlucuronosyltransferaseHumansHyperbilirubinemiaLiverNF-E2-Related Factor 2RatsBilirubinGlucuronosyltransferaseNF-E2-Related Factor 2bilirubin conjugationglucocorticoid signalingL-gulonolactone oxidaseliver organoidtransplantation

Identifiers

PMID37832542
PMCPMC10679658
OpenAlexW4387579120

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.