Bi-fated tendon-to-bone attachment cells are regulated by shared enhancers and KLF transcription factors.
cartilage
developmental biology
enthesis
mouse
musculoskeletal system
tendon
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
15 01 2021
15 01 2021
Historique:
received:
21
01
2020
accepted:
30
11
2020
entrez:
15
1
2021
pubmed:
16
1
2021
medline:
1
2
2022
Statut:
epublish
Résumé
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
Identifiants
pubmed: 33448926
doi: 10.7554/eLife.55361
pii: 55361
pmc: PMC7810463
doi:
pii:
Substances chimiques
Klf2 protein, mouse
0
Klf4 protein, mouse
0
Kruppel-Like Factor 4
0
Kruppel-Like Transcription Factors
0
Banques de données
GEO
['GSE144306', 'GSE160090']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG003988
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR055580
Pays : United States
Informations de copyright
© 2021, Kult et al.
Déclaration de conflit d'intérêts
SK, TO, MO, SM, DL, SK, RB, SB, LF, HK, TS, TC, SI, IA, AV, EZ No competing interests declared
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