Evidence map›Paper›PMID 33448926›Full record

ArticleeLife2021

Bi-fated tendon-to-bone attachment cells are regulated by shared enhancers and KLF transcription factors.

Shiri Kult, Tsviya Olender, Marco Osterwalder, Svetalana Markman, Dena Leshkowitz, Sharon Krief, Ronnie Blecher-Gonen, Shani Ben-Moshe, Lydia Farack, Hadas Keren-Shaul and 6 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. 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
5.0field-weighted citation impact, top 3% 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, 60 citations in OpenAlex.

  1. Review
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  15. KLF transcription factors in bone diseases.Journal of cellular and molecular medicine · 2024
    Review
  16. Interfacial Tissue Regeneration with Bone.Current osteoporosis reports · 2024
    Review
  17. Article
  18. Article
  19. Article
  20. 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

16 authors at 4 institutions in 3 countries.

Shiri KultDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.ORCID 0000-0001-8216-2908
Tsviya OlenderDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Marco OsterwalderEnvironmental Genomics and Systems Biology Division, Lawrence Berkeley National, Berkeley, United States.ORCID 0000-0002-1969-2313
Svetalana MarkmanDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Dena LeshkowitzLife Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel.
Sharon KriefDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Ronnie Blecher-GonenDepartment of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Shani Ben-MosheDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Lydia FarackDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.ORCID 0000-0001-9597-5078
Hadas Keren-ShaulLife Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel.
Tomer-Meir SalameLife Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel.
Terence D CapelliniDepartment of Human Evolutionary Biology, Harvard University, Department of Human Evolutionary Biology, United States; Broad Institute of Harvard and MIT, Cambridge, United States.ORCID 0000-0003-3842-8478
Shalev ItzkovitzDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.ORCID 0000-0003-0685-2522
Ido AmitDepartment of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Axel ViselEnvironmental Genomics and Systems Biology Division, Lawrence Berkeley National, Berkeley, United States.ORCID 0000-0002-4130-7784
Elazar ZelzerDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.ORCID 0000-0002-1584-6602
Weizmann Institute of Science · ILBroad Institute · USLawrence Berkeley National Laboratory · USUniversity of Bern · CH

Funding

Generation of an In Vivo Human Genome Transcriptional Enhancer DatasetR01HG003988 · NHGRI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Len Alexander Pennacchio · 2006 to 2026
$24.1M
Tendon Enthesis Development and RegenerationR01AR055580 · NIAMS · WASHINGTON UNIVERSITY · PI THOMOPOULOS, STAVROS · 2009 to 2019
$4.0M
NHGRI NIH HHS R01 HG003988NIAMS NIH HHS R01 AR055580
6 · The paper itself

Abstract

The mechanical challenge of attaching elastic tendons to stiff bones is solved by the formation of a unique transitional tissue. Here, we show that murine tendon-to-bone attachment cells are bi-fated, activating a mixture of chondrocyte and tenocyte transcriptomes, under regulation of shared regulatory elements and Krüppel-like factors (KLFs) transcription factors. High-throughput bulk and single-cell RNA sequencing of humeral attachment cells revealed expression of hundreds of chondrogenic and tenogenic genes, which was validated by in situ hybridization and single-molecule ISH. ATAC sequencing showed that attachment cells share accessible intergenic chromatin areas with either tenocytes or chondrocytes. Epigenomic analysis revealed enhancer signatures for most of these regions. Transgenic mouse enhancer reporter assays verified the shared activity of some of these enhancers. Finally, integrative chromatin and motif analyses and transcriptomic data implicated KLFs as regulators of attachment cells. Indeed, blocking expression of both

Indexed as

TranscriptomeAnimalsBone and BonesChondrocytesFemaleKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceRegulatory Sequences, Nucleic AcidTendonsTenocytesKlf2 protein, mouseKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription Factorscartilagedevelopmental biologyenthesismousemusculoskeletal systemtendon

Identifiers

PMID33448926
PMCPMC7810463
OpenAlexW3123296823

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.