Evidence map›Paper›PMID 27133796›Full record

ArticleCell stem cell2016

Genome Editing of Lineage Determinants in Human Pluripotent Stem Cells Reveals Mechanisms of Pancreatic Development and Diabetes.

Zengrong Zhu, Qing V Li, Kihyun Lee, Bess P Rosen, Federico González, Chew-Li Soh, Danwei Huangfu

Open access · bronzeAbstract read
In one paragraph

Article in Cell stem cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed
18.5field-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

117 citing papers in PubMed, 186 citations in OpenAlex.

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  6. Bone Organoids: A Novel Tool for Modeling and Managing Skeletal Disorders in Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
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57 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Zengrong ZhuDevelopmental Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
Qing V LiDevelopmental Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Kihyun LeeDevelopmental Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, 1300 York Avenue, New York, NY 10065, USA.
Bess P RosenBiochemistry, Cell and Molecular Biology Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, 1300 York Avenue, New York, NY 10065, USA.
Federico GonzálezDevelopmental Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
Chew-Li SohDevelopmental Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
Danwei HuangfuDevelopmental Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA. Electronic address: huangfud@mskcc.org.
Kettering University · USCornell University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7M
TRAINING PROGRAM IN MOLECULAR AND CELLULAR BIOLOGYT32GM008539 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI BROWN, ANTHONY M.C. · 1995 to 2020
$5.0M
Understanding Pancreatic Progenitors for Diabetes Cell-Replacement TherapyR01DK096239 · NIDDK · SLOAN-KETTERING INST CAN RESEARCH · PI HUANGFU, DANWEI · 2012 to 2021
$4.4M
NCI NIH HHS P30 CA008748NIDDK NIH HHS P30 DK020541NIDDK NIH HHS R01 DK096239NIGMS NIH HHS T32 GM008539
6 · The paper itself

Abstract

Directed differentiation of human pluripotent stem cells (hPSCs) into somatic counterparts is a valuable tool for studying disease. However, examination of developmental mechanisms in hPSCs remains challenging given complex multi-factorial actions at different stages. Here, we used TALEN and CRISPR/Cas-mediated gene editing and hPSC-directed differentiation for a systematic analysis of the roles of eight pancreatic transcription factors (PDX1, RFX6, PTF1A, GLIS3, MNX1, NGN3, HES1, and ARX). Our analysis not only verified conserved gene requirements between mice and humans but also revealed a number of previously unsuspected developmental mechanisms with implications for type 2 diabetes. These include a role of RFX6 in regulating the number of pancreatic progenitors, a haploinsufficient requirement for PDX1 in pancreatic β cell differentiation, and a potentially divergent role of NGN3 in humans and mice. Our findings support use of systematic genome editing in hPSCs as a strategy for understanding mechanisms underlying congenital disorders.

Indexed as

Gene EditingGenome, HumanBase SequenceBasic Helix-Loop-Helix ProteinsCell DifferentiationCell LineCell LineageCRISPR-Cas SystemsDiabetes MellitusGene Knockout TechniquesGlucoseHaploinsufficiencyHomeodomain ProteinsHuman Embryonic Stem CellsHumansInfant, NewbornBasic Helix-Loop-Helix ProteinsGlucoseHomeodomain ProteinsNerve Tissue ProteinsNEUROG3 protein, humanpancreatic and duodenal homeobox 1 proteinRegulatory Factor X Transcription FactorsRfx6 protein, humanTrans-Activators

Identifiers

PMID27133796
PMCPMC4892994
OpenAlexW2343240364

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.