Evidence map›Paper›PMID 24412311›Full record

ArticleCell stem cell2014

Efficient endoderm induction from human pluripotent stem cells by logically directing signals controlling lineage bifurcations.

Kyle M Loh, Lay Teng Ang, Jingyao Zhang, Vibhor Kumar, Jasmin Ang, Jun Qiang Auyeong, Kian Leong Lee, Siew Hua Choo, Christina Y Y Lim, Massimo Nichane and 13 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell stem cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 242 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
242citing papers in PubMed, 1 pooled it
12.0field-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

242 citing papers in PubMed, 1 synthesis or guideline pooled it, 443 citations in OpenAlex.

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182 more citing papers are in PubMed but not listed here.

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

23 authors at 5 institutions in 3 countries.

Kyle M LohStem Cell and Developmental Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138672, Singapore; Department of Developmental Biology, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: kyleloh@stanford.edu.
Lay Teng AngStem Cell and Developmental Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138672, Singapore. Electronic address: anglt1@gis.a-star.edu.sg.
Jingyao ZhangStem Cell and Developmental Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138672, Singapore.
Vibhor KumarStem Cell and Developmental Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138672, Singapore.
Jasmin AngStem Cell and Developmental Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138672, Singapore.
Jun Qiang AuyeongStem Cell and Developmental Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138672, Singapore.
Kian Leong LeeCancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, Singapore 117599, Singapore.
Siew Hua ChooStem Cell and Developmental Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138672, Singapore.
Christina Y Y LimStem Cell and Developmental Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138672, Singapore.
Massimo NichaneStem Cell and Developmental Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138672, Singapore.
Junru TanStem Cell and Developmental Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138672, Singapore.
Monireh Soroush NoghabiStem Cell and Developmental Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138672, Singapore.
Lisa AzzolaDepartment of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia.
Elizabeth S NgDepartment of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia; Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
Jens Durruthy-DurruthyDepartment of Developmental Biology, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Vittorio SebastianoDepartment of Developmental Biology, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lorenz PoellingerCancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, Singapore 117599, Singapore.
Andrew G ElefantyDepartment of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia; Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
Edouard G StanleyDepartment of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia; Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
Qingfeng ChenHumanized Mouse Unit, Institute of Molecular and Cell Biology, A(∗)STAR, Singapore 138673, Singapore; Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research and Technology, Singapore 138602, Singapore; Department of Microbiology, Yong Yoo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
Shyam PrabhakarStem Cell and Developmental Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138672, Singapore.
Irving L WeissmanDepartment of Developmental Biology, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Bing LimStem Cell and Developmental Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138672, Singapore; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA. Electronic address: limb1@gis.a-star.edu.sg.
Agency for Science, Technology and Research · SGRoyal Children's Hospital · AUStanford University · USNational University of Singapore · SGMonash University · AU

Funding

Interrogation of individual cells to identify progenitors and their nichesU01HL099999 · NHLBI · STANFORD UNIVERSITY · PI WEISSMAN, IRVING L. · 2009 to 2015
$7.8M
Interrogation of individual cells to identify progenitor cells and their nichesU01HL099995 · NHLBI · STANFORD UNIVERSITY · PI KRASNOW, MARK A · 2009 to 2015
$7.0M
NHLBI NIH HHS U01 HL099995NHLBI NIH HHS U01 HL099999
6 · The paper itself

Abstract

Human pluripotent stem cell (hPSC) differentiation typically yields heterogeneous populations. Knowledge of signals controlling embryonic lineage bifurcations could efficiently yield desired cell types through exclusion of alternate fates. Therefore, we revisited signals driving induction and anterior-posterior patterning of definitive endoderm to generate a coherent roadmap for endoderm differentiation. With striking temporal dynamics, BMP and Wnt initially specified anterior primitive streak (progenitor to endoderm), yet, 24 hr later, suppressed endoderm and induced mesoderm. At lineage bifurcations, cross-repressive signals separated mutually exclusive fates; TGF-β and BMP/MAPK respectively induced pancreas versus liver from endoderm by suppressing the alternate lineage. We systematically blockaded alternate fates throughout multiple consecutive bifurcations, thereby efficiently differentiating multiple hPSC lines exclusively into endoderm and its derivatives. Comprehensive transcriptional and chromatin mapping of highly pure endodermal populations revealed that endodermal enhancers existed in a surprising diversity of "pre-enhancer" states before activation, reflecting the establishment of a permissive chromatin landscape as a prelude to differentiation.

Indexed as

Cell LineageSignal TransductionAnimalsBase SequenceBody PatterningBone Morphogenetic ProteinsChromatinCulture Media, Serum-FreeDigestive SystemEmbryonic Stem CellsEndodermEnhancer Elements, GeneticEpigenesis, GeneticFibroblast Growth FactorsHumansLiverBone Morphogenetic ProteinsChromatinCulture Media, Serum-FreeFibroblast Growth FactorsTransforming Growth Factor betaWnt Proteins

Identifiers

PMID24412311
PMCPMC4045507
OpenAlexW2074884450

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.