Transcriptional landscape of aniridia-associated keratopathy through single-cell RNA sequencing

Yoshihara, Masahito; Kamuro, Rei; Hara, Susumu; Nishida, Nozomi; Ohmoto, Koji; Sasamoto, Yuzuru; Kawasaki, Satoshi; Oie, Yoshinori; Nishida, Kohji

doi:https://doi.org/10.1016/j.jtos.2025.05.008

Transcriptional landscape of aniridia-associated keratopathy through single-cell RNA sequencing

Yoshihara, Masahito; Kamuro, Rei; Hara, Susumu et al.

Ocular Surface, 2025, 38, 43-52

アクセス数:16件（2025-09-14 13:35 集計）

固定URL: https://hdl.handle.net/11094/102654

閲覧可能ファイル

ファイル	フォーマット	利用条件	サイズ	閲覧回数	利用開始日	説明	information
OculSurf_38_43	pdf	なし	95.4 MB		2026.06.07

Creative Commons : 表示 - 非営利 - 改変禁止

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

タイトル	Transcriptional landscape of aniridia-associated keratopathy through single-cell RNA sequencing
著者	NRID 1000070807065 1000070807065 researchmap permalink masahitoyoshihara masahitoyoshihara ORCID 0000-0002-8915-9282 0000-0002-8915-9282 Scopus Author ID 55817243100 55817243100 著者名 Yoshihara, Masahito
	著者名 Kamuro, Rei
	Scopus Author ID 53063707100 53063707100 NRID 1000000536956 1000000536956 researchmap permalink susumu_hara susumu_hara 著者名 Hara, Susumu
	著者名 Nishida, Nozomi
	著者名 Ohmoto, Koji
	著者名 Sasamoto, Yuzuru
	著者名 Kawasaki, Satoshi
	NRID 1000020599881 1000020599881 researchmap permalink yoshinorioie yoshinorioie Scopus Author ID 10139410100 10139410100 著者名 Oie, Yoshinori
	NRID 1000040244610 1000040244610 ORCID 0000-0001-9069-3610 0000-0001-9069-3610 researchmap permalink read0131487 read0131487 Scopus Author ID 57211973404 57211973404 著者名 Nishida, Kohji
キーワード等	Aniridia
	Cornea
	KRT12
	PAX6
	Single-cell RNA-Seq
	Transcriptome
内容	Yoshihara M., Kamuro R., Hara S., et al. Transcriptional landscape of aniridia-associated keratopathy through single-cell RNA sequencing. Ocular Surface 38, 43 (2025); https://doi.org/10.1016/j.jtos.2025.05.008.
抄録	Purpose: Aniridia-associated keratopathy (AAK) is a progressive condition characterized by conjunctivalization of the cornea, yet its molecular mechanisms remain largely unknown. This study aims to elucidate the transcriptional landscape of AAK by characterizing the gene expression profiles of corneal epithelial cells in a patient with congenital aniridia. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on epithelial tissues collected from the clear central corneal region and limbus of a 48-year-old female patient with congenital aniridia. The transcriptomic profiles were compared with those of healthy control samples. Results: scRNA-seq analysis revealed that a subpopulation of cells from the clear central corneal region expressed the cornea-specific keratins KRT3 and KRT12 despite a significant reduction in PAX6 expression. These cells exhibited corneal, conjunctival, or mixed gene signatures. Genes associated with wound healing and apoptosis were upregulated in the cornea-like cells from the aniridic cornea, indicating a chronic wound healing state. Elevated KLF4 expression and regulon activity were observed in these cornea-like cells. Most limbal epithelial cells exhibited conjunctiva-like characteristics, reflecting a loss of limbal cell identity. Conclusion: While acknowledging the limitations of a single case study, this study provides deeper insights into the transcriptional signatures associated with AAK using scRNA-seq. We identified transcriptional alterations reflecting AAK progression and highlighted potential transcription factors that may contribute to corneal identity maintenance despite PAX6 deficiency. These findings enhance our understanding of AAK and suggest potential therapeutic strategies to slow its progression.
出版者	Elsevier Inc.
収録物名	Ocular Surface
巻(号)	38
ページ	43-52
刊行年月	2025-06-07
言語	英語
ハンドルURL	https://hdl.handle.net/11094/102654
PISSN	15420124
eISSN	19375913
関連情報 (isVersionOf)	DOI (出版社版) https://doi.org/10.1016/j.jtos.2025.05.008
アクセス権	embargoed access
権利情報	© 2025. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/.
権利情報	The full-text file will be made open to the public on 7 June 2026 in accordance with the publisher's policy.
出版タイプ	Accepted Manuscript
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Ocular Surface. 2025, 38, p. 43-52
DC.title	Transcriptional landscape of aniridia-associated keratopathy through single-cell RNA sequencing
DC.creator	Yoshihara, Masahito
	Kamuro, Rei
	Hara, Susumu
	Nishida, Nozomi
	Ohmoto, Koji
	Sasamoto, Yuzuru
	Kawasaki, Satoshi
	Oie, Yoshinori
	Nishida, Kohji
DC.publisher	Elsevier Inc.
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-06-07
DC.identifier	https://doi.org/10.1016/j.jtos.2025.05.008
DC.subject	Aniridia
	Cornea
	KRT12
	PAX6
	Single-cell RNA-Seq
	Transcriptome
DC.description	Yoshihara M., Kamuro R., Hara S., et al. Transcriptional landscape of aniridia-associated keratopathy through single-cell RNA sequencing. Ocular Surface 38, 43 (2025); https://doi.org/10.1016/j.jtos.2025.05.008.
DCTERMS.abstract	Purpose: Aniridia-associated keratopathy (AAK) is a progressive condition characterized by conjunctivalization of the cornea, yet its molecular mechanisms remain largely unknown. This study aims to elucidate the transcriptional landscape of AAK by characterizing the gene expression profiles of corneal epithelial cells in a patient with congenital aniridia. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on epithelial tissues collected from the clear central corneal region and limbus of a 48-year-old female patient with congenital aniridia. The transcriptomic profiles were compared with those of healthy control samples. Results: scRNA-seq analysis revealed that a subpopulation of cells from the clear central corneal region expressed the cornea-specific keratins KRT3 and KRT12 despite a significant reduction in PAX6 expression. These cells exhibited corneal, conjunctival, or mixed gene signatures. Genes associated with wound healing and apoptosis were upregulated in the cornea-like cells from the aniridic cornea, indicating a chronic wound healing state. Elevated KLF4 expression and regulon activity were observed in these cornea-like cells. Most limbal epithelial cells exhibited conjunctiva-like characteristics, reflecting a loss of limbal cell identity. Conclusion: While acknowledging the limitations of a single case study, this study provides deeper insights into the transcriptional signatures associated with AAK using scRNA-seq. We identified transcriptional alterations reflecting AAK progression and highlighted potential transcription factors that may contribute to corneal identity maintenance despite PAX6 deficiency. These findings enhance our understanding of AAK and suggest potential therapeutic strategies to slow its progression.
DC.rights	© 2025. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/.
DC.rights	The full-text file will be made open to the public on 7 June 2026 in accordance with the publisher's policy.
DC.format	102654
citation_title	Transcriptional landscape of aniridia-associated keratopathy through single-cell RNA sequencing
citation_author	Yoshihara, Masahito
	Kamuro, Rei
	Hara, Susumu
	Nishida, Nozomi
	Ohmoto, Koji
	Sasamoto, Yuzuru
	Kawasaki, Satoshi
	Oie, Yoshinori
	Nishida, Kohji
citation_publisher	Elsevier Inc.
citation_language	英語
citation_date	2025-06-07
citation_journal_title	Ocular Surface
citation_volume	38
citation_firstpage	43
citation_lastpage	52
citation_doi	https://doi.org/10.1016/j.jtos.2025.05.008
citation_public_url	https://hdl.handle.net/11094/102654

Transcriptional landscape of aniridia-associated keratopathy through single-cell RNA sequencing

閲覧可能ファイル

論文情報

論文詳細を表示