A discrete 'early-responder' stromal-cell subtype orchestrates immunocyte recruitment to injured tissue
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc..
Following acute injury, stromal cells promote tissue regeneration by a diversity of mechanisms. Time-resolved single-cell RNA sequencing of muscle mesenchymal stromal cells (MmSCs) responding to acute injury identified an 'early-responder' subtype that spiked on day 1 and expressed a notable array of transcripts encoding immunomodulators. IL-1β, TNF-α and oncostatin M each strongly and rapidly induced MmSCs transcribing this immunomodulatory program. Macrophages amplified the program but were not strictly required for its induction. Transfer of the inflammatory MmSC subtype, tagged with a unique surface marker, into healthy hindlimb muscle induced inflammation primarily driven by neutrophils and macrophages. Among the abundant inflammatory transcripts produced by this subtype, Cxcl5 was stroma-specific and highly upregulated with injury. Depletion of this chemokine early after injury revealed a substantial impact on recruitment of neutrophils, a prolongation of inflammation to later times and an effect on tissue regeneration. Mesenchymal stromal cell subtypes expressing a comparable inflammatory program were found in a mouse model of muscular dystrophy and in several other tissues and pathologies in both mice and humans. These 'early-responder' mesenchymal stromal cells, already in place, permit rapid and coordinated mobilization and amplification of critical cell collaborators in response to injury.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
---|---|
Enthalten in: |
Nature immunology - 24(2023), 12 vom: 20. Dez., Seite 2053-2067 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Yaghi, Omar K [VerfasserIn] |
---|
Links: |
---|
Themen: |
---|
Anmerkungen: |
Date Completed 29.11.2023 Date Revised 21.02.2024 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1038/s41590-023-01669-w |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM364242647 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM364242647 | ||
003 | DE-627 | ||
005 | 20240222091441.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1038/s41590-023-01669-w |2 doi | |
028 | 5 | 2 | |a pubmed24n1301.xml |
035 | |a (DE-627)NLM364242647 | ||
035 | |a (NLM)37932455 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Yaghi, Omar K |e verfasserin |4 aut | |
245 | 1 | 2 | |a A discrete 'early-responder' stromal-cell subtype orchestrates immunocyte recruitment to injured tissue |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 29.11.2023 | ||
500 | |a Date Revised 21.02.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc. | ||
520 | |a Following acute injury, stromal cells promote tissue regeneration by a diversity of mechanisms. Time-resolved single-cell RNA sequencing of muscle mesenchymal stromal cells (MmSCs) responding to acute injury identified an 'early-responder' subtype that spiked on day 1 and expressed a notable array of transcripts encoding immunomodulators. IL-1β, TNF-α and oncostatin M each strongly and rapidly induced MmSCs transcribing this immunomodulatory program. Macrophages amplified the program but were not strictly required for its induction. Transfer of the inflammatory MmSC subtype, tagged with a unique surface marker, into healthy hindlimb muscle induced inflammation primarily driven by neutrophils and macrophages. Among the abundant inflammatory transcripts produced by this subtype, Cxcl5 was stroma-specific and highly upregulated with injury. Depletion of this chemokine early after injury revealed a substantial impact on recruitment of neutrophils, a prolongation of inflammation to later times and an effect on tissue regeneration. Mesenchymal stromal cell subtypes expressing a comparable inflammatory program were found in a mouse model of muscular dystrophy and in several other tissues and pathologies in both mice and humans. These 'early-responder' mesenchymal stromal cells, already in place, permit rapid and coordinated mobilization and amplification of critical cell collaborators in response to injury | ||
650 | 4 | |a Journal Article | |
700 | 1 | |a Hanna, Bola S |e verfasserin |4 aut | |
700 | 1 | |a Langston, P Kent |e verfasserin |4 aut | |
700 | 1 | |a Michelson, Daniel A |e verfasserin |4 aut | |
700 | 1 | |a Jayewickreme, Teshika |e verfasserin |4 aut | |
700 | 1 | |a Marin-Rodero, Miguel |e verfasserin |4 aut | |
700 | 1 | |a Benoist, Christophe |e verfasserin |4 aut | |
700 | 1 | |a Mathis, Diane |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Nature immunology |d 2000 |g 24(2023), 12 vom: 20. Dez., Seite 2053-2067 |w (DE-627)NLM10805523X |x 1529-2916 |7 nnns |
773 | 1 | 8 | |g volume:24 |g year:2023 |g number:12 |g day:20 |g month:12 |g pages:2053-2067 |
856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41590-023-01669-w |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 24 |j 2023 |e 12 |b 20 |c 12 |h 2053-2067 |