onr:"swepub:oai:DiVA.org:uu-528244"
Search: onr:"swepub:oai:DiVA.org:uu-528244" > Renal Endothelial S...
- 1 of 1
- Previous record
- Next record
- To hitlist
Renal Endothelial Single-Cell Transcriptomics Reveals Spatiotemporal Regulation and Divergent Roles of Differential Gene Transcription and Alternative Splicing in Murine Diabetic Nephropathy
-
- Zhou, Alex-Xianghua (author)
- AstraZeneca, Res & Early Dev, Cardiovasc Renal & Metab, BioPharmaceut R&D, Mölndal, Sweden.
-
- Jeansson, Marie (author)
- Karolinska Institutet,Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Huddinge, S-14152 Huddinge, Sweden
-
- He, Liqun (author)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Huddinge, S-14152 Huddinge, Sweden
- show more...
- show less...
- AstraZeneca, Res & Early Dev, Cardiovasc Renal & Metab, BioPharmaceut R&D, Mölndal, Sweden Vaskulärbiologi (creator_code:org_t)
- MDPI, 2024
- 2024
- English.
- In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 25:8
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- Endothelial cell (EC) injury is a crucial contributor to the progression of diabetic kidney disease (DKD), but the specific EC populations and mechanisms involved remain elusive. Kidney ECs (n = 5464) were collected at three timepoints from diabetic BTBRob/ob mice and non-diabetic littermates. Their heterogeneity, transcriptional changes, and alternative splicing during DKD progression were mapped using SmartSeq2 single-cell RNA sequencing (scRNAseq) and elucidated through pathway, network, and gene ontology enrichment analyses. We identified 13 distinct transcriptional EC phenotypes corresponding to different kidney vessel subtypes, confirmed through in situ hybridization and immunofluorescence. EC subtypes along nephrons displayed extensive zonation related to their functions. Differential gene expression analyses in peritubular and glomerular ECs in DKD underlined the regulation of DKD-relevant pathways including EIF2 signaling, oxidative phosphorylation, and IGF1 signaling. Importantly, this revealed the differential alteration of these pathways between the two EC subtypes and changes during disease progression. Furthermore, glomerular and peritubular ECs also displayed aberrant and dynamic alterations in alternative splicing (AS), which is strongly associated with DNA repair. Strikingly, genes displaying differential transcription or alternative splicing participate in divergent biological processes. Our study reveals the spatiotemporal regulation of gene transcription and AS linked to DKD progression, providing insight into pathomechanisms and clues to novel therapeutic targets for DKD treatment.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- diabetic nephropathy
- transcriptomics
- endothelium
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
- International Journal of Molecular Sciences (Search for host publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Zhou, Alex-Xiang ...
- Jeansson, Marie
- He, Liqun
- Wigge, Leif
- Tonelius, Pernil ...
- Tati, Ramesh
- show more...
- Cederblad, Linda
- Muhl, Lars
- Uhrbom, Martin
- Liu, Jianping
- Björnson Granqvi ...
- Lerman, Lilach O ...
- Betsholtz, Chris ...
- Hansen, Pernille ...
- show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Basic Medicine
- and Cell and Molecul ...
-
- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Clinical Medicin ...
- and Endocrinology an ...
- Articles in the publication
- International Jo ...
- By the university
- Uppsala University
- Karolinska Institutet
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
