Up-Regulation of CD146 in Schwann Cells Following Peripheral Nerve Injury Modulates Schwann Cell Function in Regeneration

Shen, Yinying; Jun, Zhu; Liu, Qianyan; Ding, Shuizi; Dun, Xin‐Peng; He, Jianghong

doi:10.3389/fncel.2021.743532

Cited by 9 publications

(5 citation statements)

References 60 publications

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“…MCAM, also known as CD146, is a membrane CAM of the immunoglobulin superfamily and functions in mammalian nervous system development 32 . MCAM also facilitates nerve regeneration and regulates cell migration and proliferation, suggesting a role for a fibroblast-neuronal axis contributing to PNS hypertrophy and activation in PN 33,34 .…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis

Patel

Joel

Lee

et al. 2023

Preprint

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Prurigo nodularis (PN) is an intensely pruritic, chronic inflammatory skin disease that disproportionately affects black patients. However, the pathogenesis of PN is poorly understood. We performed single-cell transcriptomic profiling, ligand receptor analysis and cell trajectory analysis of 28,695 lesional and non-lesional PN skin cells to uncover disease-identifying cell compositions and genetic characteristics. We uncovered a dysregulated role for fibroblasts (FBs) and myofibroblasts as a key pathogenic element in PN, which were significantly increased in PN lesional skin. We defined seven unique subclusters of FBs in PN skin and observed a shift of PN lesional FBs towards a cancer-associated fibroblast (CAF)-like phenotype, with WNT5A+ CAFs increased in the skin of PN patients and similarly so in squamous cell carcinoma (SCC). A multi-center PN cohort study subsequently revealed an increased risk of SCC as well as additional CAF-associated malignancies in PN patients, including breast and colorectal cancers. Systemic fibroproliferative diseases were also upregulated in PN patients, including renal sclerosis and idiopathic pulmonary fibrosis. Ligand receptor analyses demonstrated increased FB1-derived WNT5A and periostin interactions with neuronal receptors MCAM and ITGAV, suggesting a fibroblast-neuronal axis in PN. Type I IFN responses in immune cells and increased angiogenesis/permeability in endothelial cells were also observed. As compared to atopic dermatitis (AD) and psoriasis (PSO) patients, increased mesenchymal dysregulation is unique to PN with an intermediate Th2/Th17 phenotype between atopic dermatitis and psoriasis. These findings identify a pathogenic role for CAFs in PN, including a novel targetable WNT5A+ fibroblast subpopulation and CAF-associated malignancies in PN patients.

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Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis

Patel

Joel

Lee

et al. 2023

Preprint

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show abstract

“…MCAM, also known as CD146, is a membrane CAM of the immunoglobulin superfamily and functions in mammalian nervous system development 33 . MCAM also facilitates nerve regeneration and regulates cell migration and proliferation, suggesting a role for a fibroblast-neuronal axis contributing to PNS hypertrophy and activation in PN 34,35 .…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis

Kwatra,

Patel,

Joel

et al. 2023

Preprint

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Background: Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. Methods: We performed single-cell transcriptomic profiling of 28,695 lesional and non-lesional PN cells. Results: Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted towards a cancer-associated fibroblast (CAF)-like phenotype, with POSTN+WNT5A+ CAFs increased in PN, and similarly so in squamous cell carcinoma. A multi-center cohort study revealed an increased risk of SCC and CAF-associated malignancies (breast and colorectal) in PN patients. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in PN patients. Ligand receptor analyses demonstrated a fibroblast neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors MCAM and ITGAV. Compared to atopic dermatitis and psoriasis, mesenchymal dysregulation is unique to PN with an intermediate Th2/Th17 phenotype. Conclusion: These findings identify a pathogenic and targetable POSTN+WNT5A+ fibroblast subpopulation that may predispose CAF-associated malignancies in PN patients.

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“…Interestingly, the CD146 molecule may have an impact on peripheral nerve regeneration. Shen et al [ 136 ] suggested that CD146 not only had a key role in promoting of blood vessel regeneration but also regulated cell migration. Functional assessments showed that knockdown of CD146 decreased proliferation and viability of Schwann cells but increased their migration.…”

Section: Markers For Specialized Populations Within Mscsmentioning

confidence: 99%

“…Functional assessments showed that knockdown of CD146 decreased proliferation and viability of Schwann cells but increased their migration. Additionally, CD146 was upregulated in Schwann cells and cells associated with blood vessels following mouse peripheral nerve injury [ 136 ]. Taking together described CD146+ cells properties and its key role in vascular endothelial cell activity and angiogenesis, this subpopulation could be used in vascular smooth muscle, endothelial, or IVDs regeneration.…”

Section: Markers For Specialized Populations Within Mscsmentioning

confidence: 99%

Promising Markers in the Context of Mesenchymal Stem/Stromal Cells Subpopulations with Unique Properties

Smolinska,

Bzinkowska,

Rybkowska

et al. 2023

Stem Cells International

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The heterogeneity of the mesenchymal stem/stromal cells (MSCs) population poses a challenge to researchers and clinicians, especially those observed at the population level. What is more, the lack of precise evidences regarding MSCs developmental origin even further complicate this issue. As the available evidences indicate several possible pathways of MSCs formation, this diverse origin may be reflected in the unique subsets of cells found within the MSCs population. Such populations differ in specialization degree, proliferation, and immunomodulatory properties or exhibit other additional properties such as increased angiogenesis capacity. In this review article, we attempted to identify such outstanding populations according to the specific surface antigens or intracellular markers. Described groups were characterized depending on their specialization and potential therapeutic application. The reports presented here cover a wide variety of properties found in the recent literature, which is quite scarce for many candidates mentioned in this article. Even though the collected information would allow for better targeting of specific subpopulations in regenerative medicine to increase the effectiveness of MSC-based therapies.

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Up-Regulation of CD146 in Schwann Cells Following Peripheral Nerve Injury Modulates Schwann Cell Function in Regeneration

Cited by 9 publications

References 60 publications

Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis

Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis

Single-cell RNA sequencing reveals dysregulated fibroblast subclusters in prurigo nodularis

Promising Markers in the Context of Mesenchymal Stem/Stromal Cells Subpopulations with Unique Properties

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