Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis

Jay R. Patel; Marina Z. Joel; Kevin K. Lee; Anusha Kambala; Hannah Cornman; Olusola Oladipo; Matthew Taylor; Brenda Umenita Imo; Emily Z. Ma; Jaya Manjunath; Alexander L. Kollhoff; June Deng; Varsha Parthasarathy; Karen Cravero; Melika Marani; Mindy Szeto; Ryan Zhao; Sreenidhi Sankararaman; Ruixiang Li; Shanae Henry; Thomas Pritchard; Vito Rebecca; Madan M. Kwatra; Won Jin Ho; Xinzhong Dong; Sewon Kang; Shawn G. Kwatra

doi:10.1016/j.jid.2023.12.021

Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis

Jay R. Patel, Marina Z. Joel, Kevin K. Lee, Anusha Kambala, Hannah Cornman, Olusola Oladipo, Matthew Taylor, Brenda Umenita Imo, Emily Z. Ma, Jaya Manjunath, Alexander L. Kollhoff, June Deng, Varsha Parthasarathy, Karen Cravero, Melika Marani, Mindy Szeto, Ryan Zhao, Sreenidhi Sankararaman, Ruixiang Li, Shanae HenryThomas Pritchard, Vito Rebecca, Madan M. Kwatra, Won Jin Ho, Xinzhong Dong, Sewon Kang, Shawn G. Kwatra

Research output: Contribution to journal › Article › peer-review

Abstract

Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. We performed single-cell transcriptomic profiling of 28,695 lesional and nonlesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted toward a cancer-associated FB–like phenotype, with POSTN+WNT5A+ cancer-associated FBs increased in PN and similarly so in squamous cell carcinoma. A multicenter cohort study revealed an increased risk of squamous cell carcinoma and cancer-associated FB–associated malignancies (breast and colorectal) in patients with PN. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in patients with PN. Ligand–receptor analyses demonstrated an FB neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors melanoma cell adhesion molecule and ITGAV. These findings identify a pathogenic and targetable POSTN+WNT5A+ FB subpopulation that may predispose cancer-associated FB–associated malignancies in patients with PN.

Original language	English (US)
Pages (from-to)	1568-1578.e5
Journal	Journal of Investigative Dermatology
Volume	144
Issue number	7
DOIs	https://doi.org/10.1016/j.jid.2023.12.021
State	Published - Jul 2024

Keywords

Fibroblasts
Periostin
Prurigo nodularis
WNT5A
scRNAseq

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Dermatology
Cell Biology

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10.1016/j.jid.2023.12.021

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Patel, J. R., Joel, M. Z., Lee, K. K., Kambala, A., Cornman, H., Oladipo, O., Taylor, M., Imo, B. U., Ma, E. Z., Manjunath, J., Kollhoff, A. L., Deng, J., Parthasarathy, V., Cravero, K., Marani, M., Szeto, M., Zhao, R., Sankararaman, S., Li, R., ... Kwatra, S. G. (2024). Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis. Journal of Investigative Dermatology, 144(7), 1568-1578.e5. https://doi.org/10.1016/j.jid.2023.12.021

Patel, JR, Joel, MZ, Lee, KK, Kambala, A, Cornman, H, Oladipo, O, Taylor, M, Imo, BU, Ma, EZ, Manjunath, J, Kollhoff, AL, Deng, J, Parthasarathy, V, Cravero, K, Marani, M, Szeto, M, Zhao, R, Sankararaman, S, Li, R, Henry, S, Pritchard, T, Rebecca, V, Kwatra, MM, Ho, WJ , Dong, X , Kang, S & Kwatra, SG 2024, 'Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis', Journal of Investigative Dermatology, vol. 144, no. 7, pp. 1568-1578.e5. https://doi.org/10.1016/j.jid.2023.12.021

@article{c2c4140bf5804665b7e84cc1c01573cf,

title = "Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis",

abstract = "Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. We performed single-cell transcriptomic profiling of 28,695 lesional and nonlesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted toward a cancer-associated FB–like phenotype, with POSTN+WNT5A+ cancer-associated FBs increased in PN and similarly so in squamous cell carcinoma. A multicenter cohort study revealed an increased risk of squamous cell carcinoma and cancer-associated FB–associated malignancies (breast and colorectal) in patients with PN. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in patients with PN. Ligand–receptor analyses demonstrated an FB neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors melanoma cell adhesion molecule and ITGAV. These findings identify a pathogenic and targetable POSTN+WNT5A+ FB subpopulation that may predispose cancer-associated FB–associated malignancies in patients with PN.",

keywords = "Fibroblasts, Periostin, Prurigo nodularis, WNT5A, scRNAseq",

author = "Patel, {Jay R.} and Joel, {Marina Z.} and Lee, {Kevin K.} and Anusha Kambala and Hannah Cornman and Olusola Oladipo and Matthew Taylor and Imo, {Brenda Umenita} and Ma, {Emily Z.} and Jaya Manjunath and Kollhoff, {Alexander L.} and June Deng and Varsha Parthasarathy and Karen Cravero and Melika Marani and Mindy Szeto and Ryan Zhao and Sreenidhi Sankararaman and Ruixiang Li and Shanae Henry and Thomas Pritchard and Vito Rebecca and Kwatra, {Madan M.} and Ho, {Won Jin} and Xinzhong Dong and Sewon Kang and Kwatra, {Shawn G.}",

note = "Publisher Copyright: {\textcopyright} 2024",

year = "2024",

month = jul,

doi = "10.1016/j.jid.2023.12.021",

language = "English (US)",

volume = "144",

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T1 - Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis

AU - Patel, Jay R.

AU - Joel, Marina Z.

AU - Lee, Kevin K.

AU - Kambala, Anusha

AU - Cornman, Hannah

AU - Oladipo, Olusola

AU - Taylor, Matthew

AU - Imo, Brenda Umenita

AU - Ma, Emily Z.

AU - Manjunath, Jaya

AU - Kollhoff, Alexander L.

AU - Deng, June

AU - Parthasarathy, Varsha

AU - Cravero, Karen

AU - Marani, Melika

AU - Szeto, Mindy

AU - Zhao, Ryan

AU - Sankararaman, Sreenidhi

AU - Li, Ruixiang

AU - Henry, Shanae

AU - Pritchard, Thomas

AU - Rebecca, Vito

AU - Kwatra, Madan M.

AU - Ho, Won Jin

AU - Dong, Xinzhong

AU - Kang, Sewon

AU - Kwatra, Shawn G.

PY - 2024/7

Y1 - 2024/7

N2 - Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. We performed single-cell transcriptomic profiling of 28,695 lesional and nonlesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted toward a cancer-associated FB–like phenotype, with POSTN+WNT5A+ cancer-associated FBs increased in PN and similarly so in squamous cell carcinoma. A multicenter cohort study revealed an increased risk of squamous cell carcinoma and cancer-associated FB–associated malignancies (breast and colorectal) in patients with PN. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in patients with PN. Ligand–receptor analyses demonstrated an FB neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors melanoma cell adhesion molecule and ITGAV. These findings identify a pathogenic and targetable POSTN+WNT5A+ FB subpopulation that may predispose cancer-associated FB–associated malignancies in patients with PN.

AB - Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. We performed single-cell transcriptomic profiling of 28,695 lesional and nonlesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted toward a cancer-associated FB–like phenotype, with POSTN+WNT5A+ cancer-associated FBs increased in PN and similarly so in squamous cell carcinoma. A multicenter cohort study revealed an increased risk of squamous cell carcinoma and cancer-associated FB–associated malignancies (breast and colorectal) in patients with PN. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in patients with PN. Ligand–receptor analyses demonstrated an FB neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors melanoma cell adhesion molecule and ITGAV. These findings identify a pathogenic and targetable POSTN+WNT5A+ FB subpopulation that may predispose cancer-associated FB–associated malignancies in patients with PN.

KW - Fibroblasts

KW - Periostin

KW - Prurigo nodularis

KW - WNT5A

KW - scRNAseq

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DO - 10.1016/j.jid.2023.12.021

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C2 - 38246584

AN - SCOPUS:85186315235

SN - 0022-202X

VL - 144

SP - 1568-1578.e5

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 7

ER -

Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis

Abstract

Keywords

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