Evidence map›Paper›PMID 31390551›Full record

ArticleCell metabolism2019

Generation of Human Fatty Livers Using Custom-Engineered Induced Pluripotent Stem Cells with Modifiable SIRT1 Metabolism.

Alexandra Collin de l'Hortet, Kazuki Takeishi, Jorge Guzman-Lepe, Kazutoyo Morita, Abhinav Achreja, Branimir Popovic, Yang Wang, Kan Handa, Anjali Mittal, Noah Meurs and 7 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
12.6field-weighted citation impact, top 1% 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

57 citing papers in PubMed, 101 citations in OpenAlex.

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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

17 authors at 5 institutions in 4 countries.

Alexandra Collin de l'HortetDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Kazuki TakeishiDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Jorge Guzman-LepeDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Kazutoyo MoritaDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Abhinav AchrejaDepartment of Biomedical Engineering, University of Michigan Biomedical Engineering, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Branimir PopovicDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Yang WangDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China.
Kan HandaDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Anjali MittalBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.
Noah MeursDepartment of Biomedical Engineering, University of Michigan Biomedical Engineering, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Ziwen ZhuDepartment of Biomedical Engineering, University of Michigan Biomedical Engineering, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Frank WeinbergDivision of Hematology/Oncology, Department of Internal Medicine, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
Michael SalomonSirion Biotech, Am Klopferspitz 19, 82152 Planegg, Germany.
Ira J FoxDepartment of Surgery, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA, USA.
Chu-Xia DengFaculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau, China.
Deepak NagrathDepartment of Biomedical Engineering, University of Michigan Biomedical Engineering, Ann Arbor, MI, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Alejandro Soto-GutierrezDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: als208@pitt.edu.
University of Pittsburgh · USUniversity of Michigan–Ann Arbor · USBioSurfaces (United States) · USKyushu University · JPUniversity of Macau · MO

Funding

Pittsburgh Liver Research CenterP30DK120531 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DAVID A GELLER · 2019 to 2026
$10.9M
Mini-Livers Derived from Human IPS Cells for Modeling Steatosis and TherapyR01DK099257 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NAGRATH, DEEPAK, SOTO-GUTIERREZ, ALEJANDRO · 2014 to 2024
$3.4M
Applying a Human Liver Microphysiology System to Develop Therapeutic Strategies for Non-Alcoholic Fatty Liver Disease (NAFLD)R01DK117881 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, D. LANSING · 2018 to 2021
$2.7M
Targeting Stromal Influences on Glutamine Addiction in Ovarian CancerR01CA227622 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MOK, SAMUEL C, NAGRATH, DEEPAK · 2018 to 2022
$2.3M
Human Microphysiology Systems Disease Model of Type 2 Diabetes Starting with Liver and pancreatic IsletsUG3DK119973 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, D. LANSING · 2018 to 2019
$2.3M
Identification of USP13 as a therapeutic target for ovarian cancerR01CA222251 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI LU, XIONGBIN, NAGRATH, DEEPAK · 2018 to 2022
$1.8M
Uncovering Role of Exosomes in Regulating Pancreatic Cancer Cell MetabolismR01CA204969 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NAGRATH, DEEPAK · 2017 to 2021
$1.7M
NCI NIH HHS R01 CA204969NCI NIH HHS R01 CA222251NCI NIH HHS R01 CA227622NIDDK NIH HHS P30 DK120531NIDDK NIH HHS R01 DK099257NIDDK NIH HHS R01 DK117881NIDDK NIH HHS UG3 DK119973
6 · The paper itself

Abstract

The mechanisms by which steatosis of the liver progresses to non-alcoholic steatohepatitis and end-stage liver disease remain elusive. Metabolic derangements in hepatocytes controlled by SIRT1 play a role in the development of fatty liver in inbred animals. The ability to perform similar studies using human tissue has been limited by the genetic variability in man. We generated human induced pluripotent stem cells (iPSCs) with controllable expression of SIRT1. By differentiating edited iPSCs into hepatocytes and knocking down SIRT1, we found increased fatty acid biosynthesis that exacerbates fat accumulation. To model human fatty livers, we repopulated decellularized rat livers with human mesenchymal cells, fibroblasts, macrophages, and human SIRT1 knockdown iPSC-derived hepatocytes and found that the human iPSC-derived liver tissue developed macrosteatosis, acquired proinflammatory phenotype, and shared a similar lipid and metabolic profiling to human fatty livers. Biofabrication of genetically edited human liver tissue may become an important tool for investigating human liver biology and disease.

Indexed as

Cell EngineeringAdultAnimalsCell DifferentiationCells, CulturedFatty AcidsFatty LiverHumansMalePluripotent Stem CellsRatsRats, Sprague-DawleySirtuin 1Fatty AcidsSIRT1 protein, humanSirtuin 1cellular engineeringhepatic differentiationhuman fatty liverhuman iPSCsliver metabolismNAFLDNASHSIRT1

Identifiers

PMID31390551
PMCPMC6691905
OpenAlexW2965996124

What OpenQuestion holds

Textmetadata
LicenceTDM
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.