Transcriptional and temporal heterogeneity of developing α cells revealed by single-cell RNA sequencing

Shimizu, Naoya; Taguchi, Tomomi; Himuro, Miwa; Shimomura, Iichiro; Lynn, Francis C.; Watada, Hirotaka; Sasaki, Shugo; Miyatsuka, Takeshi

doi:https://doi.org/10.1016/j.bbrc.2025.152996

Transcriptional and temporal heterogeneity of developing α cells revealed by single-cell RNA sequencing

Shimizu, Naoya; Taguchi, Tomomi; Himuro, Miwa et al.

Biochemical and Biophysical Research Communications, 2025, 792, 152996

アクセス数:29件（2025-12-11 12:56 集計）

固定URL: https://hdl.handle.net/11094/103325

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タイトル	Transcriptional and temporal heterogeneity of developing α cells revealed by single-cell RNA sequencing
著者	著者名 Shimizu, Naoya
	NRID 1000070907138 1000070907138 著者名 Taguchi, Tomomi
	NRID 1000010896301 1000010896301 著者名 Himuro, Miwa
	NRID 1000060346145 1000060346145 ORCID 0000-0002-0851-9603 0000-0002-0851-9603 researchmap permalink shimomura_i shimomura_i Scopus Author ID 7006715546 7006715546 著者名 Shimomura, Iichiro
	著者名 Lynn, Francis C.
	NRID 1000060343480 1000060343480 著者名 Watada, Hirotaka
	NRID 1000060908185 1000060908185 ORCID 0000-0002-3696-7809 0000-0002-3696-7809 researchmap permalink shugosasaki shugosasaki Scopus Author ID 55427278100 55427278100 著者名 Sasaki, Shugo
	NRID 1000060622363 1000060622363 著者名 Miyatsuka, Takeshi
キーワード等	Endocrine progenitors
	Pancreatic α cell
	Single-cell RNA sequencing
	α cell genesis
内容	Shimizu N., Taguchi T., Himuro M., et al. Transcriptional and temporal heterogeneity of developing α cells revealed by single-cell RNA sequencing. Biochemical and Biophysical Research Communications 792, 152996 (2025); https://doi.org/10.1016/j.bbrc.2025.152996.
抄録	Glucagon (Gcg)-expressing pancreatic α cells play pivotal roles in maintaining glucose and amino acid homeostasis; however, the cellular heterogeneity during α-cell genesis remains unclear. To explore the transcriptional dynamics of developing α cells, single-cell transcriptomics was performed using “Gcg-Timer” embryos, in which newly generated α cells can be sorted from more differentiated α cells by their fluorescence. Green-fluorescent early α cells expressed high levels of key β-cell genes, such as Ins1, Ins2, and Pcsk1, as well as other endocrine-specific mRNAs, including Sst and Ghrl, whereas green/red double-fluorescent late α cells expressed higher levels of Gcg, suggesting temporal maturation during α-cell differentiation. Furthermore, comprehensive analyses of the Gcg-Timer dataset and two independent datasets at different developmental stages revealed that mitochondrial transcripts were more robustly expressed in α cells than in developing β cells. Taken together, single-cell transcriptomics using a time-resolved reporter mouse line demonstrated novel features of temporal and transcriptional heterogeneity of developing α cells.
出版者	Elsevier B.V.
収録物名	Biochemical and Biophysical Research Communications
巻(号)	792
ページ	152996
刊行年月	2025-12-15
言語	英語
ハンドルURL	https://hdl.handle.net/11094/103325
PISSN	0006291X
eISSN	10902104
関連情報 (isVersionOf)	DOI (出版社版) https://doi.org/10.1016/j.bbrc.2025.152996
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 15 December 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	Biochemical and Biophysical Research Communications. 2025, 792, p. 152996
DC.title	Transcriptional and temporal heterogeneity of developing α cells revealed by single-cell RNA sequencing
DC.creator	Shimizu, Naoya
	Taguchi, Tomomi
	Himuro, Miwa
	Shimomura, Iichiro
	Lynn, Francis C.
	Watada, Hirotaka
	Sasaki, Shugo
	Miyatsuka, Takeshi
DC.publisher	Elsevier B.V.
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-12-15
DC.identifier	https://doi.org/10.1016/j.bbrc.2025.152996
DC.subject	Endocrine progenitors
	Pancreatic α cell
	Single-cell RNA sequencing
	α cell genesis
DC.description	Shimizu N., Taguchi T., Himuro M., et al. Transcriptional and temporal heterogeneity of developing α cells revealed by single-cell RNA sequencing. Biochemical and Biophysical Research Communications 792, 152996 (2025); https://doi.org/10.1016/j.bbrc.2025.152996.
DCTERMS.abstract	Glucagon (Gcg)-expressing pancreatic α cells play pivotal roles in maintaining glucose and amino acid homeostasis; however, the cellular heterogeneity during α-cell genesis remains unclear. To explore the transcriptional dynamics of developing α cells, single-cell transcriptomics was performed using “Gcg-Timer” embryos, in which newly generated α cells can be sorted from more differentiated α cells by their fluorescence. Green-fluorescent early α cells expressed high levels of key β-cell genes, such as Ins1, Ins2, and Pcsk1, as well as other endocrine-specific mRNAs, including Sst and Ghrl, whereas green/red double-fluorescent late α cells expressed higher levels of Gcg, suggesting temporal maturation during α-cell differentiation. Furthermore, comprehensive analyses of the Gcg-Timer dataset and two independent datasets at different developmental stages revealed that mitochondrial transcripts were more robustly expressed in α cells than in developing β cells. Taken together, single-cell transcriptomics using a time-resolved reporter mouse line demonstrated novel features of temporal and transcriptional heterogeneity of developing α cells.
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 15 December 2026 in accordance with the publisher's policy.
DC.format	103325
citation_title	Transcriptional and temporal heterogeneity of developing α cells revealed by single-cell RNA sequencing
citation_author	Shimizu, Naoya
	Taguchi, Tomomi
	Himuro, Miwa
	Shimomura, Iichiro
	Lynn, Francis C.
	Watada, Hirotaka
	Sasaki, Shugo
	Miyatsuka, Takeshi
citation_publisher	Elsevier B.V.
citation_language	英語
citation_date	2025-12-15
citation_journal_title	Biochemical and Biophysical Research Communications
citation_volume	792
citation_firstpage	152996
citation_doi	https://doi.org/10.1016/j.bbrc.2025.152996
citation_public_url	https://hdl.handle.net/11094/103325

Transcriptional and temporal heterogeneity of developing α cells revealed by single-cell RNA sequencing

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