Origin and diversification of fibroblasts from the sclerotome in zebrafish

Roger, Christine; Kocha, Katrinka M.; Méndez-Olivos, Emilio E.; Ruel, Tyler D.; Huang, Peng

doi:10.1016/j.ydbio.2023.03.004

Cited by 9 publications

(22 citation statements)

References 67 publications

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“…These included three known sclerotome-derived fibroblast populations: fin mesenchymal cells, tenocytes, and stromal reticular cells. As expected, the ‘fin mesenchymal cell’ cluster was labelled by genes previously identified in fin cells ( Kln1 , and1 , and2 ; Table S2) ( 26 , 30 , 32 , 33 ) and known to be important for zebrafish fin development.…”

Section: Resultssupporting

confidence: 73%

“…S3B). In addition to sclerotome-derived fibroblasts, we also identified minor populations of muscle, myotome, and periderm populations, which have been previously observed in nkx3-1 NTR-mCherry fish ( 30 ) (Figs. 1B, S2, Table S1).…”

Section: Resultssupporting

confidence: 68%

“…1B, S2, Table S1). Based on expression of reported marker genes for the sclerotome ( postnb , twist1b , matn4 , tgKi ) and its derivatives ( 24 , 28 , 30 ), we identified seven clusters comprising 1756 cells arising from the sclerotome: Scl1-7 (Figs. 1B, S3).…”

Section: Resultsmentioning

confidence: 99%

“…1E, S4A, S4B). Similarly, the ‘tenocyte’ cluster was labelled by known tenocyte genes ( scxa, cilp ; Table S2) ( 22 , 30 ), and all three top candidate markers tested ( col22a1 , cilp , prelp ) showed specific expression in fibroblasts along the myotendinous junction (MTJ) (Figs. 1E, S4A, S4C).…”

Section: Resultsmentioning

confidence: 99%

“…In our previous work, we established the homeobox transcripKon factor gene nkx3.1 as a specific sclerotome marker in zebrafish 24,30 . Using the nkx3.1:Gal4; UAS:NTR-mCherry transgenic line (nkx3.1 NTR-mCherry , similar designaKons are used for all Gal4/UAS lines), we demonstrated that the sclerotome compartment of the somite gives rise to mulKple fibroblast populaKons in the trunk, including tendon fibroblasts (tenocytes), fin mesenchymal cells in the fin fold, blood vessel-associated fibroblasts, and intersKKal fibroblasts 24,27,30 . To determine whether these fibroblast subtypes represent transcripKonally unique cell populaKons, we performed single-cell RNA sequencing (scRNA-seq) on cells derived from the nkx3.1 lineage.…”

Section: Scrna-seq Analysis Of the Sclerotome Lineagementioning

confidence: 99%

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Single-cell analysis reveals distinct fibroblast plasticity during tenocyte regeneration in zebrafish

Rajan

Rosin

Labit

et al. 2023

Preprint

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Despite their importance in tissue maintenance and repair, fibroblast diversity and plasticity are poorly understood. Using single-cell RNA sequencing, we uncover six distinct sclerotome-derived fibroblast populations in the zebrafish trunk, including progenitor-like perivascular/interstitial fibroblasts, and specialized fibroblasts such as tenocytes. To determine fibroblast plasticity in vivo, we develop a tendon regeneration model. Lineage tracing reveals that laser-ablated tenocytes can be quickly regenerated by pre-existing fibroblasts. Combining live imaging and clonal analysis, we demonstrate that perivascular/interstitial fibroblasts actively migrate to the injury site, where they proliferate and give rise to new tenocytes. Strikingly, other specialized fibroblast subtypes derived from the same sclerotome lineage, including uninjured tenocytes, show no regenerative response. Interestingly, active Hedgehog (Hh) signaling is required for the proliferation and differentiation of activated fibroblasts. Together, our work highlights the functional diversity of fibroblasts and establishes perivascular/interstitial fibroblasts as tenocyte progenitors that promote tendon regeneration in a Hh signaling-dependent manner.

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Section: Resultssupporting

confidence: 73%

Section: Resultssupporting

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Scrna-seq Analysis Of the Sclerotome Lineagementioning

confidence: 99%

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Single-cell analysis reveals distinct fibroblast plasticity during tenocyte regeneration in zebrafish

Rajan

Rosin

Labit

et al. 2023

Preprint

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Identification of distinct vascular mural cell populations during zebrafish embryonic development

Colijn,

Nambara,

Malin

et al. 2023

Developmental Dynamics

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BackgroundMural cells are an essential perivascular cell population that associate with blood vessels and contribute to vascular stabilization and tone. In the embryonic zebrafish vasculature, pdgfrb and tagln are commonly used as markers for identifying pericytes and vascular smooth muscle cells. However, the overlapping and distinct expression patterns of these markers in tandem have not been fully described.ResultsHere, we used the Tg(pdgfrb:Gal4FF; UAS:RFP) and Tg(tagln:NLS‐EGFP) transgenic lines to identify single‐ and double‐positive perivascular cell populations on the cranial, axial, and intersegmental vessels between 1 and 5 days postfertilization. From this comparative analysis, we discovered two novel regions of tagln‐positive cell populations that have the potential to function as mural cell precursors. Specifically, we found that the hypochord—a reportedly transient structure—contributes to tagln‐positive cells along the dorsal aorta. We also identified a unique mural cell progenitor population that resides along the midline between the neural tube and notochord and contributes to intersegmental vessel mural cell coverage.ConclusionTogether, our findings highlight the variability and versatility of tracking both pdgfrb and tagln expression in mural cells of the developing zebrafish embryo and reveal unexpected embryonic cell populations that express pdgfrb and tagln.

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The development of brain pericytes requires expression of the transcription factornkx3.1in intermediate precursors

Childs

Ahuja

Adjekukor

et al. 2023

Preprint

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Brain pericytes are critical for regulating endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. The genetic pathways guiding undifferentiated cells into maturepericytes are not well understood. We show here that precursor populations from both neural crest and head mesoderm express the transcription factor nkx3.1 develop into brain pericytes. We identify the gene signature of these precursors, and show that an nkx3.1, foxf2a, and cxcl12b-expressing pericyte precursor population is present around the basilar artery prior to artery formation and pericyte recruitment. The precursors later spread throughout the brain and differentiate to express canonical pericyte markers. Cxcl12b- Cxcr4 signaling is required for pericyte attachment and differentiation. Further, both nkx3.1 and cxcl12b are necessary and sufficient in regulating pericyte number as loss inhibits and gain increases pericyte number. Through genetic experiments we have defined a precursor population for brain pericytes and identified genes critical for their differentiation.

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Origin and diversification of fibroblasts from the sclerotome in zebrafish

Cited by 9 publications

References 67 publications

Single-cell analysis reveals distinct fibroblast plasticity during tenocyte regeneration in zebrafish

Single-cell analysis reveals distinct fibroblast plasticity during tenocyte regeneration in zebrafish

Identification of distinct vascular mural cell populations during zebrafish embryonic development

The development of brain pericytes requires expression of the transcription factornkx3.1in intermediate precursors

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