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Renal Endothelial S...
Renal Endothelial Single-Cell Transcriptomics Reveals Spatiotemporal Regulation and Divergent Roles of Differential Gene Transcription and Alternative Splicing in Murine Diabetic Nephropathy
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- Zhou, Alex-Xianghua (författare)
- AstraZeneca, Res & Early Dev, Cardiovasc Renal & Metab, BioPharmaceut R&D, Mölndal, Sweden.
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- Jeansson, Marie (författare)
- Karolinska Institutet,Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Huddinge, S-14152 Huddinge, Sweden
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- He, Liqun (författare)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Huddinge, S-14152 Huddinge, Sweden
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- Wigge, Leif (författare)
- AstraZeneca, Data Sci & Quantitat Biol, Discovery Sci, Biopharmaceut R&D, S-43183 Mölndal, Sweden.
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- Tonelius, Pernilla (författare)
- AstraZeneca, Res & Early Dev, Cardiovasc Renal & Metab, BioPharmaceut R&D, Mölndal, Sweden.
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- Tati, Ramesh (författare)
- AstraZeneca, Res & Early Dev, Cardiovasc Renal & Metab, BioPharmaceut R&D, Mölndal, Sweden.
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- Cederblad, Linda (författare)
- AstraZeneca, Res & Early Dev, Cardiovasc Renal & Metab, BioPharmaceut R&D, Mölndal, Sweden.
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- Muhl, Lars (författare)
- Karolinska Institutet,Karolinska Inst, Dept Med Huddinge, S-14152 Huddinge, Sweden.
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- Uhrbom, Martin (författare)
- AstraZeneca, Res & Early Dev, Cardiovasc Renal & Metab, BioPharmaceut R&D, Mölndal, Sweden.;Karolinska Inst, Dept Med Huddinge, S-14152 Huddinge, Sweden.
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- Liu, Jianping (författare)
- Karolinska Institutet,Karolinska Inst, Dept Med Huddinge, S-14152 Huddinge, Sweden.
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- Björnson Granqvist, Anna (författare)
- AstraZeneca, Res & Early Dev, Cardiovasc Renal & Metab, BioPharmaceut R&D, Mölndal, Sweden.
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- Lerman, Lilach O. (författare)
- Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55902 USA.
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- Betsholtz, Christer (författare)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Huddinge, S-14152 Huddinge, Sweden
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- Hansen, Pernille B. L. (författare)
- AstraZeneca, Res & Early Dev, Cardiovasc Renal & Metab, BioPharmaceut R&D, Mölndal, Sweden.
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AstraZeneca, Res & Early Dev, Cardiovasc Renal & Metab, BioPharmaceut R&D, Mölndal, Sweden Vaskulärbiologi (creator_code:org_t)
- MDPI, 2024
- 2024
- Engelska.
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 25:8
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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http://kipublication...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- 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)
Nyckelord
- diabetic nephropathy
- transcriptomics
- endothelium
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Zhou, Alex-Xiang ...
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Jeansson, Marie
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He, Liqun
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Wigge, Leif
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Tonelius, Pernil ...
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Tati, Ramesh
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visa fler...
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Cederblad, Linda
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Muhl, Lars
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Uhrbom, Martin
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Liu, Jianping
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Björnson Granqvi ...
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Lerman, Lilach O ...
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Betsholtz, Chris ...
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Hansen, Pernille ...
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Uppsala universitet
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Karolinska Institutet