foxc1 is required for embryonic head vascular smooth muscle differentiation in zebrafish

Whitesell, Thomas R.; Chrystal, Paul; Ryu, Jae-Ryeon; Munsie, Nicole; Grosse, Ann S.; French, Curtis R.; Workentine, Matthew L.; Li, Rui; Zhu, Lihua Julie; Waskiewicz, Andrew J.; Lehmann, Ordan J.; Lawson, Nathan D.; Childs, Sarah J.

doi:10.1016/j.ydbio.2019.06.005

Cited by 49 publications

(56 citation statements)

References 82 publications

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“…All protocols were approved by the Animal Care Committee at the University of Calgary (#AC17-0128). The following transgenic strains were utilized in this study: TgBAC(col1a2:Gal4)ca102 (46, 49), TgBAC(col1a2:GFP)ca103 (46), Tg(kdrl:EGFP)la116 (72), Tg(kdrl:mCherry)ci5 (73), TgBAC(nkx3.1:Gal4)ca101 (46), TgBAC(pdgfrb:Gal4FF)ca42 (45,74), TgBAC(pdgfrb:GFP)ca41 (45), Tg(UAS:Kaede)s1999t (75), Tg(UAS:NTR-mCherry)c264 (75). The mosaic col1a2:Gal4; UAS:Kaede line was maintained by growing embryos with more mosaic Kaede expression.…”

Section: Methodsmentioning

confidence: 99%

Dual function of perivascular fibroblasts in vascular stabilization in zebrafish

Rajan

Roger

Kocha

et al. 2020

Preprint

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24Blood vessels are vital to sustain life in all vertebrates. While it is known that mural cells (pericytes 25 and smooth muscle cells) regulate vascular integrity, the contribution of other cell types to vascular 26 stabilization has been largely unexplored. Using zebrafish, we identified sclerotome-derived 27 perivascular fibroblasts as a novel population of blood vessel associated cells. In contrast to pericytes, 28 perivascular fibroblasts emerge early during development, express the extracellular matrix (ECM) 29 genes col1a2 and col5a1, and display distinct morphology and distribution. Time-lapse imaging 30 reveals that perivascular fibroblasts serve as pericyte precursors. Genetic ablation of perivascular 31 fibroblasts results in dysmorphic blood vessels with variable diameters. Strikingly, col5a1 mutants 32show spontaneous hemorrhage, and the penetrance of the phenotype is strongly enhanced by the 33 additional loss of col1a2. Together, our work reveals dual roles of perivascular fibroblasts in vascular 34 stabilization where they establish the ECM around nascent vessels and function as pericyte 35 progenitors. 36 3 AUTHOR SUMMARY 37 38 Blood vessels are essential to sustain life in humans. Defects in blood vessels can lead to serious 39 diseases, such as hemorrhage, tissue ischemia, and stroke. However, how blood vessel stability is 40 maintained by surrounding support cells is still poorly understood. Using the zebrafish model, we 41 identify a new population of blood vessel associated cells termed perivascular fibroblasts, which 42 originate from the sclerotome, an embryonic structure that is previously known to generate the 43 skeleton of the animal. Perivascular fibroblasts are distinct from pericytes, a known population of 44 blood vessel support cells. They become associated with blood vessels much earlier than pericytes 45 and express several collagen genes, encoding main components of the extracellular matrix. Loss of 46 perivascular fibroblasts or mutations in collagen genes result in fragile blood vessels prone to 47 53 54The vascular system is crucial to the survival of vertebrates. Blood vessels must rapidly expand 55 and contract in response to systemic cues, but also maintain the stability to withstand the stress of 56 blood flow. To maintain their integrity, blood vessels are supported by a highly specialized 57 perivascular architecture comprised of blood vessel associated cells and the surrounding extracellular 58 matrix (ECM) (1,2). Compromised vascular integrity can result in devastating human diseases, such 59 as aneurysms, vascular malformations, and hemorrhagic strokes (3-6). However, how blood vessels 60 are stabilized by different perivascular components is still poorly understood. 61The prevailing model is that vascular stability is maintained at three different levels: endothelial 62 cells, mural cells and the surrounding ECM (2). First, blood vessels are lined by endothelial cells. 63Adherens and tight junctions between endothelial cells provide the primary barrier to passage o...

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Section: Methodsmentioning

confidence: 99%

Dual function of perivascular fibroblasts in vascular stabilization in zebrafish

Rajan

Roger

Kocha

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Platelet derived growth factor (PDGF) signaling is known to play an important role in pericyte recruitment and the platelet derived growth factor receptor-beta (pdgfrb) is a well-established pericyte marker [43,45,46]. We utilized the pdgfrb:GFP [47] and pdgfrb:Gal4FF; UAS:NTR-mCherry (referred to as pdgfrb NTR-mCherry ) [48] lines to label pericytes. Interestingly, while both pdgfrb:GFP and pdgfrb NTR-mCherry lines labeled pericytes (GFP high mCherry + expression) at 4 dpf, pdgfrb:GFP but not pdgfrb NTR-mCherry also marked perivascular fibroblasts (GFP low mCherryexpression) at 2 and 4 dpf (days post fertilization) (S3A and S3B Fig).…”

Section: Perivascular Fibroblasts Are Distinct From Pericytesmentioning

confidence: 99%

“…All protocols were approved by the Animal Care Committee at the University of Calgary (#AC17-0128). The following transgenic strains were utilized in this study: TgBAC(col1a2:Gal4)ca102 [44,50], TgBAC(col1a2:GFP)ca103 [44], Tg(kdrl:EGFP)la116 [73], Tg(kdrl:mCherry)ci5 [74], TgBAC(nkx3.1:Gal4)ca101 [44], TgBAC(pdgfrb:Gal4FF)ca42 [48], TgBAC(pdgfrb:GFP)ca41 [47], Tg(UAS:Col1a2-GFP)ca111, Tg(UAS:Kaede)s1999t [75], and Tg(UAS:NTR-mCherry)c264 [75]. The mosaic col1a2:Gal4; UAS:Kaede line was maintained by growing embryos with more mosaic Kaede expression.…”

Section: Zebrafish Strainsmentioning

confidence: 99%

Dual function of perivascular fibroblasts in vascular stabilization in zebrafish

et al. 2020

View full text Add to dashboard Cite

Blood vessels are vital to sustain life in all vertebrates. While it is known that mural cells (pericytes and smooth muscle cells) regulate vascular integrity, the contribution of other cell types to vascular stabilization has been largely unexplored. Using zebrafish, we identified sclerotome-derived perivascular fibroblasts as a novel population of blood vessel associated cells. In contrast to pericytes, perivascular fibroblasts emerge early during development, express the extracellular matrix (ECM) genes col1a2 and col5a1, and display distinct morphology and distribution. Time-lapse imaging reveals that perivascular fibroblasts serve as pericyte precursors. Genetic ablation of perivascular fibroblasts markedly reduces collagen deposition around endothelial cells, resulting in dysmorphic blood vessels with variable diameters. Strikingly, col5a1 mutants show spontaneous hemorrhage, and the penetrance of the phenotype is strongly enhanced by the additional loss of col1a2. Together, our work reveals dual roles of perivascular fibroblasts in vascular stabilization where they establish the ECM around nascent vessels and function as pericyte progenitors.

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“…We have previously used RNA-seq to profile endothelial cell gene expression in zebrafish embryos (Quillien et al, 2017;Whitesell et al, 2019). In unpublished observations from those studies, we noted discrepancies between identical datasets separately quantified using Ensembl (version 95, hereafter referred to as Ens95) and RefSeq (GCF_000002035.6_GRCz11) transcriptome annotations.…”

Section: Discrepancies In Rna-seq Analysis Between Zebrafish Ensemblmentioning

confidence: 99%

An improved zebrafish transcriptome annotation for sensitive and comprehensive detection of cell type-specific genes

Lawson

Shin

et al. 2020

eLife

Self Cite

116

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The zebrafish is ideal for studying embryogenesis and is increasingly applied to model human disease. In these contexts, RNA-sequencing (RNA-seq) provides mechanistic insights by identifying transcriptome changes between experimental conditions. Application of RNA-seq relies on accurate transcript annotation for a genome of interest. Here, we find discrepancies in analysis from RNA-seq datasets quantified using Ensembl and RefSeq zebrafish annotations. These issues were due, in part, to variably annotated 3' untranslated regions and thousands of gene models missing from each annotation. Since these discrepancies could compromise downstream analyses and biological reproducibility, we built a more comprehensive zebrafish transcriptome annotation that addresses these deficiencies. Our annotation improves detection of cell type-specific genes in both bulk and single cell RNA-seq datasets, where it also improves resolution of cell clustering. Thus, we demonstrate that our new transcriptome annotation can outperform existing annotations, providing an important resource for zebrafish researchers.

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foxc1 is required for embryonic head vascular smooth muscle differentiation in zebrafish

Cited by 49 publications

References 82 publications

Dual function of perivascular fibroblasts in vascular stabilization in zebrafish

Dual function of perivascular fibroblasts in vascular stabilization in zebrafish

Dual function of perivascular fibroblasts in vascular stabilization in zebrafish

An improved zebrafish transcriptome annotation for sensitive and comprehensive detection of cell type-specific genes

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