ptx3a+ fibroblast/epicardial cells provide a transient macrophage niche to promote heart regeneration

Sun, Jisheng; Peterson, Elizabeth A.; Chen, Xin; Wang, Jinhu

doi:10.1016/j.celrep.2024.114092

Cited by 2 publications

(1 citation statement)

References 114 publications

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“…Our RNAseq data show significant downregulation of several transcripts known to be expressed by injury-responsive infiltrating fibroblasts including orthologs of fstl1, cthrc1 , and ptx3 (Fig. 3A) 21,27,28 . These data also show that Wnt inhibition leads to significant downregulation of two paralogous genes encoding the homeodomain transcription factor Prrx1, which has previously been implicated in fibroblast-mediated tissue regeneration (Fig.…”

Section: Resultsmentioning

confidence: 86%

Transcriptomic analysis identifies injury-responsive fibroblast populations as potential mediators of Wnt-dependent spinal cord regeneration

Alper,

Vasudevan,

Wheeler

et al. 2024

Preprint

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Background: In humans and other mammals, spinal cord injury (SCI) can lead to a permanent loss of sensory and motor function, due to the inability of damaged neurons and axons to regenerate. However, other vertebrate species including zebrafish exhibit complete spinal cord regeneration and functional recovery after SCI. Wnt signaling is required for neurogenesis and axon regrowth in a larval zebrafish SCI model, but the genes regulated by this pathway and the cell types that express them remain largely unknown. Results: In this study, we used bulk RNA-sequencing (RNAseq) to identify candidate genes regulated by Wnt signaling that are expressed after SCI. Using this unbiased screen, we identified multiple genes previously unassociated with SCI in larval zebrafish, and confirmed by in situ hybridization that their expression is both injury-responsive and Wnt-dependent. Conclusions: Together, our data suggest novel gene targets and cell types that may play important roles in spinal cord regeneration.

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Section: Resultsmentioning

confidence: 86%

Transcriptomic analysis identifies injury-responsive fibroblast populations as potential mediators of Wnt-dependent spinal cord regeneration

Alper,

Vasudevan,

Wheeler

et al. 2024

Preprint

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Cross-species single-cell RNA-seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injury

Cortada,

Yao,

Xia

et al. 2024

Commun Biol

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The immune system coordinates the response to cardiac injury and controls regenerative and fibrotic scar outcomes in the heart and subsequent chronic low-grade inflammation associated with heart failure. Adult mice and humans lack the ability to fully recover while adult zebrafish spontaneously regenerate after heart injury. Here we profile the inflammatory response to heart cryoinjury in zebrafish and coronary artery ligation in mouse using single cell transcriptomics. We interrogate the extracardiac reaction to cardiomyocyte necrosis to assess the specific peripheral tissue and immune cell reaction to chronic stress. Cardiac macrophages play a critical role in determining tissue homeostasis by healing versus scarring. We identify distinct transcriptional clusters of monocytes/macrophages (mono/Mϕ) in each species and find analogous pairs in zebrafish and mice. However, the reaction to myocardial injury is largely disparate between mice and zebrafish. The dichotomous response to heart damage between the murine and zebrafish mono/Mϕ and/or the presence of distinct zebrafish mono/Mϕ subtypes may underlie the impaired regenerative process in adult mammals and humans. Our study furnishes a direct cross-species comparison of immune responses between regenerative and profibrotic myocardial injury models, providing a useful resource to the fields of regenerative biology and cardiovascular research.

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ptx3a+ fibroblast/epicardial cells provide a transient macrophage niche to promote heart regeneration

Cited by 2 publications

References 114 publications

Transcriptomic analysis identifies injury-responsive fibroblast populations as potential mediators of Wnt-dependent spinal cord regeneration

Transcriptomic analysis identifies injury-responsive fibroblast populations as potential mediators of Wnt-dependent spinal cord regeneration

Cross-species single-cell RNA-seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injury

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