Evidence map›Paper›PMID 27183470›Full record

ArticleNature cell biology2016

Medial HOXA genes demarcate haematopoietic stem cell fate during human development.

Diana R Dou, Vincenzo Calvanese, Maria I Sierra, Andrew T Nguyen, Arazin Minasian, Pamela Saarikoski, Rajkumar Sasidharan, Christina M Ramirez, Jerome A Zack, Gay M Crooks and 2 more

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

Article in Nature cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

78 citing papers in PubMed, 100 citations in OpenAlex.

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18 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

12 authors at 1 institution in 1 country.

Diana R DouDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA.
Vincenzo CalvaneseDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA.ORCID 0000-0002-7937-1511
Maria I SierraDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA.
Andrew T NguyenDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA.
Arazin MinasianDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA.
Pamela SaarikoskiDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA.
Rajkumar SasidharanDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA.
Christina M RamirezDepartment of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California 90095, USA.
Jerome A ZackEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, California 90095, USA.
Gay M CrooksDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA.
Zoran GalicEli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, California 90095, USA.
Hanna K A MikkolaDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA.
University of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTON, PETER A · 1991 to 2018
$39.9M
UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
Transduction of Human Stem and Progenitor CellsP01HL073104 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOHN, DONALD B · 2003 to 2013
$18.3M
Human Embryonic Stem Cell CoreP01GM081621 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZACK, JEROME A. · 2008 to 2012
$9.3M
Training in Developmental HematologyT32HL086345 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KOHN, DONALD B · 2007 to 2022
$3.8M
Defining the Self-Renewal Program in Human Hematopoietic Stem CellsR01DK100959 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MIKKOLA, HANNA KATRI ANNIKKI · 2014 to 2022
$2.9M
NCI NIH HHS P30 CA016042NHLBI NIH HHS P01 HL073104NHLBI NIH HHS T32 HL086345NIAID NIH HHS P30 AI028697NIDDK NIH HHS R01 DK100959NIGMS NIH HHS P01 GM081621NIGMS NIH HHS T32 GM007185
6 · The paper itself

Abstract

Pluripotent stem cells (PSCs) may provide a potential source of haematopoietic stem/progenitor cells (HSPCs) for transplantation; however, unknown molecular barriers prevent the self-renewal of PSC-HSPCs. Using two-step differentiation, human embryonic stem cells (hESCs) differentiated in vitro into multipotent haematopoietic cells that had the CD34(+)CD38(-/lo)CD90(+)CD45(+)GPI-80(+) fetal liver (FL) HSPC immunophenotype, but exhibited poor expansion potential and engraftment ability. Transcriptome analysis of immunophenotypic hESC-HSPCs revealed that, despite their molecular resemblance to FL-HSPCs, medial HOXA genes remained suppressed. Knockdown of HOXA7 disrupted FL-HSPC function and caused transcriptome dysregulation that resembled hESC-derived progenitors. Overexpression of medial HOXA genes prolonged FL-HSPC maintenance but was insufficient to confer self-renewal to hESC-HSPCs. Stimulation of retinoic acid signalling during endothelial-to-haematopoietic transition induced the HOXA cluster and other HSC/definitive haemogenic endothelium genes, and prolonged HSPC maintenance in culture. Thus, medial HOXA gene expression induced by retinoic acid signalling marks the establishment of the definitive HSPC fate and controls HSPC identity and function.

Indexed as

Cell LineageAntigens, CD34Cell DifferentiationCells, CulturedGene Expression ProfilingGenes, HomeoboxHematopoietic Stem CellsHomeodomain ProteinsHumansLeukocyte Common AntigensMultipotent Stem CellsTranscriptomeAntigens, CD34Homeodomain ProteinsHoxA proteinLeukocyte Common AntigensPTPRC protein, human

Identifiers

PMID27183470
PMCPMC4981340
OpenAlexW2403002878

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.