Evidence map›Paper›PMID 26585277›Full record

ArticleCurrent biology : CB2015

Fas-Activated Mitochondrial Apoptosis Culls Stalled Embryonic Stem Cells to Promote Differentiation.

Eric S Wang, Nichole A Reyes, Collin Melton, Noelle E Huskey, Olga Momcilovic, Andrei Goga, Robert Blelloch, Scott A Oakes

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

Article in Current biology : CB, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

10 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Context-dependent roles of YAP/TAZ in stem cell fates and cancer.Cellular and molecular life sciences : CMLS · 2021
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
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

8 authors at 2 institutions in 1 country.

Eric S WangDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
Nichole A ReyesDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
Collin MeltonDepartment of Urology, University of California, San Francisco, San Francisco, CA 94143, USA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Noelle E HuskeyDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
Olga MomcilovicDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
Andrei GogaDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Robert BlellochDepartment of Urology, University of California, San Francisco, San Francisco, CA 94143, USA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: blellochr@stemcell.ucsf.edu.
Scott A OakesDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: scott.oakes@ucsf.edu.
University of California, San Francisco · USUCSF Helen Diller Family Comprehensive Cancer Center · US

Funding

UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Holger Willenbring · 1986 to 2026
$30.7M
Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRUMMEL, MATTHEW F · 2003 to 2019
$21.8M
Project 4: Human Endometrial Programming for Successful ImplantationP50HD055764 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GIUDICE, LINDA C · 2014 to 2022
$16.4M
PREDOCTORAL TRAINING IN BIOMEDICAL SCIENCEST32GM008568 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANSEL, KARL MARK · 1995 to 2019
$6.3M
Targeting the MYC Oncogene with CDK InhibitorsR01CA136717 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOGA, ANDREI · 2010 to 2014
$1.8M
Signaling Cell Death from the Endoplasmic ReticulumR01CA136577 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI OAKES, SCOTT A. · 2009 to 2013
$1.6M
Attenuating ER and oxidative stress signaling to reduce cell degeneration in vivoR01DK095306 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI OAKES, SCOTT A., PAPA, FEROZ R · 2013 to 2016
$1.5M
MicroRNA Based Pathway Discovery in Cellular ReprogrammingR01GM101180 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BLELLOCH, ROBERT · 2012 to 2015
$1.4M
Determining the role of IRE1alpha in amyotrophic lateral sclerosisF31NS083323 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WANG, ERIC · 2013 to 2013
$36k
Howard Hughes Medical InstituteNCI NIH HHS R01 CA136577NCI NIH HHS R01CA136577NCI NIH HHS R01 CA136717NCI NIH HHS R01CA136717NICHD NIH HHS P50 HD055764NIDDK NIH HHS P30 DK026743NIDDK NIH HHS P30 DK063720NIDDK NIH HHS R01 DK095306NIDDK NIH HHS R01DK095306NIGMS NIH HHS R01 GM101180NIGMS NIH HHS R01GM101180NIGMS NIH HHS T32 GM008568NINDS NIH HHS F31 NS083323NINDS NIH HHS F31NS083323NINDS NIH HHS F31NS626272
6 · The paper itself

Abstract

The intrinsic (mitochondrial) apoptotic pathway is a conserved cell death program crucial for eliminating superfluous, damaged, or incorrectly specified cells, and the multi-domain pro-death BCL-2 family proteins BAX and BAK are required for its activation. In response to internal damage or developmental signals, BAX and/or BAK permeabilize the mitochondrial outer membrane, resulting in cytochrome c release and activation of effector caspases such as Caspase-3 (Casp3). While the mitochondrial apoptotic pathway plays a critical role during late embryonic development in mammals, its role during early development remains controversial. Here, we show that Bax(-/-)Bak(-/-) murine embryonic stem cells (ESCs) display defects during the exit from pluripotency, both in culture and during teratoma formation. Specifically, we find that when ESCs are stimulated to differentiate, a subpopulation fails to do so and instead upregulates FAS in a p53-dependent manner to trigger Bax/Bak-dependent apoptosis. Blocking this apoptotic pathway prevents the removal of these poorly differentiated cells, resulting in the retention of cells that have not exited pluripotency. Taken together, our results provide further evidence for heterogeneity in the potential of ESCs to successfully differentiate and reveal a novel role for apoptosis in promoting efficient ESC differentiation by culling cells that are slow to exit pluripotency.

Indexed as

ApoptosisCell DifferentiationAnimalsEmbryonic Stem Cellsfas ReceptorMiceMitochondriaSignal TransductionFas protein, mousefas Receptor

Identifiers

PMID26585277
PMCPMC4703423
OpenAlexW2180840482

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.