Evidence map›Paper›PMID 23395001›Full record

ArticleMolecular cell2013

Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells.

Philipp B Staber, Pu Zhang, Min Ye, Robert S Welner, César Nombela-Arrieta, Christian Bach, Marc Kerenyi, Boris A Bartholdy, Hong Zhang, Meritxell Alberich-Jordà and 12 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
9.0field-weighted citation impact, top 2% 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

92 citing papers in PubMed, 162 citations in OpenAlex.

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32 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

22 authors at 9 institutions in 5 countries.

Philipp B StaberHarvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA. pstaber@bidmc.harvard.edu
Pu Zhang
Min Ye
Robert S Welner
César Nombela-Arrieta
Christian Bach
Marc Kerenyi
Boris A Bartholdy
Hong Zhang
Meritxell Alberich-Jordà
Sanghoon Lee
Henry Yang
Felicia Ng
Junyan Zhang
Mathias Leddin
Leslie E Silberstein
Gerald Hoefler
Stuart H Orkin
Berthold Göttgens
Frank Rosenbauer
Gang Huang
Daniel G Tenen
Harvard University · USHarvard Stem Cell Institute · USMax Delbrück Center · DENational University of Singapore · SGWellcome/MRC Cambridge Stem Cell Institute · GBBoston Children's Hospital · USCincinnati Children's Hospital Medical Center · USMedical University of Graz · ATNational University Cancer Institute, Singapore · SG

Funding

MOLECULAR BIOLOGY OF MYELOID DIFFERENTIATIONR01CA041456 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI TENEN, DANIEL G · 1986 to 2010
$4.6M
Molecular biology of myeloid differentiationR01HL112719 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI TENEN, DANIEL G · 2012 to 2015
$2.2M
Cancer Research UK 12765Howard Hughes Medical InstituteMedical Research Council MC_PC_12009National Centre for the Replacement, Refinement and Reduction of Animals in Research G0900729/1NCI NIH HHS R01 CA041456NHLBI NIH HHS R01 HL112719NHLBI NIH HHS R01HL112719Wellcome Trust 079249Wellcome Trust 100140
6 · The paper itself

Abstract

To provide a lifelong supply of blood cells, hematopoietic stem cells (HSCs) need to carefully balance both self-renewing cell divisions and quiescence. Although several regulators that control this mechanism have been identified, we demonstrate that the transcription factor PU.1 acts upstream of these regulators. So far, attempts to uncover PU.1's role in HSC biology have failed because of the technical limitations of complete loss-of-function models. With the use of hypomorphic mice with decreased PU.1 levels specifically in phenotypic HSCs, we found reduced HSC long-term repopulation potential that could be rescued completely by restoring PU.1 levels. PU.1 prevented excessive HSC division and exhaustion by controlling the transcription of multiple cell-cycle regulators. Levels of PU.1 were sustained through autoregulatory PU.1 binding to an upstream enhancer that formed an active looped chromosome architecture in HSCs. These results establish that PU.1 mediates chromosome looping and functions as a master regulator of HSC proliferation.

Indexed as

Cell DifferentiationAdult Stem CellsAnimalsCell CycleCell ProliferationHematopoietic Stem CellsHumansMiceMice, Inbred StrainsProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Trans-ActivatorsProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Trans-Activators

Identifiers

PMID23395001
PMCPMC3644723
OpenAlexW1991817025

What OpenQuestion holds

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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.