Evidence map›Paper›PMID 27210748›Full record

ArticleCell reports2016

Discovery of a Small-Molecule BMP Sensitizer for Human Embryonic Stem Cell Differentiation.

Lingling Feng, Brandoch Cook, Su-Yi Tsai, Ting Zhou, Brooke LaFlamme, Todd Evans, Shuibing Chen

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

20 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
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  4. Review
  5. Article
  6. Emerging role of BMPs/BMPR2 signaling pathway in treatment for pulmonary fibrosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024
    Review
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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

7 authors at 1 institution in 2 countries.

Lingling FengKey Laboratory of Pesticide and Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079, China; Department of Surgery, Weill Cornell Medical College, New York, NY 10065, USA.
Brandoch CookDepartment of Surgery, Weill Cornell Medical College, New York, NY 10065, USA.
Su-Yi TsaiDepartment of Surgery, Weill Cornell Medical College, New York, NY 10065, USA.
Ting ZhouDepartment of Surgery, Weill Cornell Medical College, New York, NY 10065, USA.
Brooke LaFlammeDepartment of Surgery, Weill Cornell Medical College, New York, NY 10065, USA.
Todd EvansDepartment of Surgery, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: tre2003@med.cornell.edu.
Shuibing ChenDepartment of Surgery, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: shc2034@med.cornell.edu.
Cornell University · US

Funding

Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI JEFFREY E. PESSIN · 2015 to 2026
$27.7M
Regulation of Embryonic Erythropoiesis by BMP SignalingR37HL056182 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI EVANS, TODD R · 2009 to 2016
$3.2M
Regulation of Embryonic Erythropoiesis by BMP SignalingR01HL056182 · NHLBI · YESHIVA UNIVERSITY · PI EVANS, TODD R · 1997 to 2008
$3.1M
Studying the Progression and Regression of Beta Cell Dysfunction in Type 2 DiabetDP2DK098093 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHEN, SHUIBING · 2012 to 2017
$2.6M
A molecular pathway controlling cardiomyocyte specification.R01HL111400 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI EVANS, TODD R · 2012 to 2016
$2.1M
Discovery of BMP-dependent mechanisms controlling embryonic hematopoiesisK01DK096031 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI COOK, BRANDOCH D · 2013 to 2017
$437k
NHLBI NIH HHS R01 HL056182NHLBI NIH HHS R01 HL111400NHLBI NIH HHS R37 HL056182NIDDK NIH HHS DP2 DK098093NIDDK NIH HHS K01 DK096031NIDDK NIH HHS P30 DK020541
6 · The paper itself

Abstract

Sorely missing from the "toolkit" for directed differentiation of stem/progenitor cells are agonists of the BMP-signaling pathway. Using a high-throughput chemical screen, we discovered that PD407824, a checkpoint kinase 1 (CHK1) inhibitor, increases the sensitivity of cells to sub-threshold amounts of BMP4. We show utility of the compound in the directed differentiation of human embryonic stem cells toward mesoderm or cytotrophoblast stem cells. Blocking CHK1 activity using pharmacological compounds or CHK1 knockout using single guide RNA (sgRNA) confirmed that CHK1 inhibition increases the sensitivity to BMP4 treatment. Additional mechanistic studies indicate that CHK1 inhibition depletes p21 levels, thereby activating CDK8/9, which then phosphorylates the SMAD2/3 linker region, leading to decreased levels of SMAD2/3 protein and enhanced levels of nuclear SMAD1. This study provides insight into mechanisms controlling the BMP/transforming growth factor beta (TGF-β) signaling pathways and a useful pharmacological reagent for directed differentiation of stem cells.

Indexed as

Cell DifferentiationAnimalsBone Morphogenetic Protein 4CarbazolesCell LineageCellular ReprogrammingCheckpoint Kinase 1Human Embryonic Stem CellsHumansMesodermMiceModels, BiologicalMyoblastsOsteoblastsSignal TransductionSmad ProteinsBone Morphogenetic Protein 4CarbazolesCheckpoint Kinase 1PD 407824Smad ProteinsSmall Molecule Libraries

Identifiers

PMID27210748
PMCPMC4889468
OpenAlexW2402446210

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.