Evidence map›Paper›PMID 35452598›Full record

ArticleCell stem cell2022

The nuclear receptor THRB facilitates differentiation of human PSCs into more mature hepatocytes.

Haiting Ma, Esmée de Zwaan, Yang Eric Guo, Paloma Cejas, Prathapan Thiru, Martijn van de Bunt, Jacob F Jeppesen, Sudeepa Syamala, Alessandra Dall'Agnese, Brian J Abraham and 7 more

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

16 citing papers in PubMed, 28 citations in OpenAlex.

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  15. A decade of liver organoids: Advances in disease modeling.Clinical and molecular hepatology · 2023
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 1 country.

Haiting MaWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Esmée de ZwaanWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Yang Eric GuoWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Paloma CejasCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Prathapan ThiruWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Martijn van de BuntGlobal Drug Discovery, Novo Nordisk, Cambridge, MA 02142, USA.
Jacob F JeppesenWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Global Drug Discovery, Novo Nordisk, Cambridge, MA 02142, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Sudeepa SyamalaCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Alessandra Dall'AgneseWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Brian J AbrahamWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Computational Biology, St Jude Children's Research Hospital, Memphis, TN, USA.
Dongdong FuWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Carrie Garrett-EngeleWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Tong Ihn LeeWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Henry W LongCenter for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Linda G GriffithDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Richard A YoungWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Rudolf JaenischWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: jaenisch@wi.mit.edu.
Whitehead Institute for Biomedical Research · USHarvard University · USDana-Farber Cancer Institute · USMassachusetts Institute of Technology · USNovo Nordisk (United States) · US

Funding

An iPSC based platform for functionally assessing genetic and environmental riskR01NS088538 · NINDS · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF, MYERS, RICHARD H · 2014 to 2018
$5.0M
NINDS NIH HHS R01 NS088538
6 · The paper itself

Abstract

To understand the mechanisms regulating the in vitro maturation of hPSC-derived hepatocytes, we developed a 3D differentiation system and compared gene regulatory elements in human primary hepatocytes with those in hPSC-hepatocytes that were differentiated in 2D or 3D conditions by RNA-seq, ATAC-seq, and H3K27Ac ChIP-seq. Regulome comparisons showed a reduced enrichment of thyroid receptor THRB motifs in accessible chromatin and active enhancers without a reduced transcription of THRB. The addition of thyroid hormone T3 increased the binding of THRB to the CYP3A4 proximal enhancer, restored the super-enhancer status and gene expression of NFIC, and reduced the expression of AFP. The resultant hPSC-hepatocytes showed gene expression, epigenetic status, and super-enhancer landscape closer to primary hepatocytes and activated regulatory regions including non-coding SNPs associated with liver-related diseases. Transplanting the hPSC-hepatocytes resulted in the engraftment of human hepatocytes into the mouse liver without disrupting normal liver histology. This work implicates the environmental factor-nuclear receptor axis in regulating the maturation of hPSC-hepatocytes.

Indexed as

ChromatinHepatocytesAnimalsCell DifferentiationHumansMicePolymorphism, Single NucleotideReceptors, Cytoplasmic and NuclearRegulatory Sequences, Nucleic AcidChromatinReceptors, Cytoplasmic and Nuclear3D cultureepigeneticshepatocytes differentiation and maturationhuman pluripotent stem cellsnuclear receptorspBAFtranscriptional regulation

Identifiers

PMID35452598
PMCPMC9466295
OpenAlexW4224232645

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.