Evidence map›Paper›PMID 26936319›Full record

ArticleNature communications2016

Single-cell differences in matrix gene expression do not predict matrix deposition.

Allison J Cote, Claire M McLeod, Megan J Farrell, Patrick D McClanahan, Margaret C Dunagin, Arjun Raj, Robert L Mauck

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

36 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Article
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  4. Spatial transcriptomic applications in orthopedics.Connective tissue research · 2025
    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 2 institutions in 1 country.

Allison J CoteDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Claire M McLeodDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Megan J FarrellDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Patrick D McClanahanDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Margaret C DunaginDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Arjun RajDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Robert L MauckDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
University of Pennsylvania · USPhiladelphia VA Medical Center · US

Funding

TRAINING PROGRAM IN CELL AND MOLECULAR BIOLOGYT32GM007229 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BARTOLOMEI, MARISA S. · 1985 to 2023
$14.0M
Multidisciplinary Training in Cardiovascular BiologyT32HL007954 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DAVIES, PETER FRANCIS · 2000 to 2019
$9.9M
Penn Dermatology Research Training ProgramT32AR007465 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI Elizabeth Anne Grice, David Joel Margolis · 1986 to 2026
$9.0M
The Role of Hyaluronic Acid Receptors in Tendon HealingP30AR050950 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI ELLIOTT, DAWN M · 2006 to 2015
$6.2M
Multi-scale biomechanics of engineered and native fibrous load-bearing tissueR01EB002425 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI ELLIOTT, DAWN M, MAUCK, ROBERT L · 2003 to 2017
$4.1M
Engineering Developmental Microenvironments: Cartilage Formation and MaturationR01EB008722 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI BURDICK, JASON A, MAUCK, ROBERT L · 2009 to 2017
$3.0M
A Comprehensive Spatial Picture of Transcription in the NucleusDP2OD008514 · OD · UNIVERSITY OF PENNSYLVANIA · PI RAJ, ARJUN · 2011 to 2011
$2.4M
NHLBI NIH HHS T32 HL007954NIAMS NIH HHS P30 AR050950NIAMS NIH HHS T32 AR007465NIBIB NIH HHS R01 EB002425NIBIB NIH HHS R01 EB008722NIBIB NIH HHS R01EB008722NIBIB NIH HHS R01 EB02425NIGMS NIH HHS T32 GM007229NIGMS NIH HHS T32 GM-07229NIH HHS 1DP2OD008514NIH HHS DP2 OD008514
6 · The paper itself

Abstract

Mesenchymal stem cells (MSCs) display substantial cell-to-cell heterogeneity, complicating their use in regenerative medicine. However, conventional bulk assays mask this variability. Here we show that both chondrocytes and chondrogenically induced MSCs exhibit substantial mRNA expression heterogeneity. Single-molecule RNA FISH to measure mRNA expression of differentiation markers in single cells reveals that sister cell pairs have high levels of mRNA variability, suggesting that marker expression is not heritable. Surprisingly, this variability does not correlate with cell-to-cell differences in cartilage-like matrix production. Transcriptome-wide analysis suggests that no combination of markers can predict functional potential. De-differentiating chondrocytes also show a disconnect between mRNA expression of the cartilage marker aggrecan and cartilage-like matrix accumulation. Altogether, these quantitative analyses suggest that sorting subpopulations based on these markers would only marginally enrich the progenitor population for 'superior' MSCs. Our results suggest that instantaneous mRNA abundance of canonical markers is tenuously linked to the chondrogenic phenotype at the single-cell level.

Indexed as

AnimalsBiomarkersCattleCell DifferentiationChondrocytesExtracellular MatrixGene Expression RegulationIn Situ Hybridization, FluorescenceMesenchymal Stem CellsRNA, MessengerBiomarkersRNA, Messenger

Identifiers

PMID26936319
PMCPMC4782061
OpenAlexW2295897051

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.