Single-cell sequencing dissects the transcriptional identity of activated fibroblasts and identifies novel persistent distal tubular injury patterns in kidney fibrosis Article Swipe
Valeria Rudman-Melnick
,
Mike Adam
,
Kaitlynn Stowers
,
Andrew Potter
,
Qing Ma
,
Saagar M. Chokshi
,
Davy Vanhoutte
,
Íñigo Valiente-Alandí
,
Diana M. Lindquist
,
Michelle L. Nieman
,
Matthew Kofron
,
Eunah Chung
,
Joo‐Seop Park
,
S. Steven Potter
,
Prasad Devarajan
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-023-50195-0
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1038/s41598-023-50195-0
Examining kidney fibrosis is crucial for mechanistic understanding and developing targeted strategies against chronic kidney disease (CKD). Persistent fibroblast activation and tubular epithelial cell (TEC) injury are key CKD contributors. However, cellular and transcriptional landscapes of CKD and specific activated kidney fibroblast clusters remain elusive. Here, we analyzed single cell transcriptomic profiles of two clinically relevant kidney fibrosis models which induced robust kidney parenchymal remodeling. We dissected the molecular and cellular landscapes of kidney stroma and newly identified three distinctive fibroblast clusters with “secretory”, “contractile” and “vascular” transcriptional enrichments. Also, both injuries generated failed repair TECs (frTECs) characterized by decline of mature epithelial markers and elevation of stromal and injury markers. Notably, frTECs shared transcriptional identity with distal nephron segments of the embryonic kidney. Moreover, we identified that both models exhibited robust and previously unrecognized distal spatial pattern of TEC injury, outlined by persistent elevation of renal TEC injury markers including Krt8 and Vcam1, while the surviving proximal tubules (PTs) showed restored transcriptional signature. We also found that long-term kidney injuries activated a prominent nephrogenic signature, including Sox4 and Hox gene elevation, which prevailed in the distal tubular segments. Our findings might advance understanding of and targeted intervention in fibrotic kidney disease.
Related Topics
Concepts
Kidney
Kidney disease
Fibrosis
Biology
Acute kidney injury
Stromal cell
Nephron
Fibroblast
Kidney development
Fibroblast growth factor 23
Pathology
Cancer research
Cell biology
Medicine
Internal medicine
Embryonic stem cell
Endocrinology
Gene
Parathyroid hormone
Cell culture
Genetics
Calcium
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41598-023-50195-0
- https://www.nature.com/articles/s41598-023-50195-0.pdf
- OA Status
- gold
- Cited By
- 18
- References
- 73
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4390571770
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4390571770Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41598-023-50195-0Digital Object Identifier
- Title
-
Single-cell sequencing dissects the transcriptional identity of activated fibroblasts and identifies novel persistent distal tubular injury patterns in kidney fibrosisWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-01-03Full publication date if available
- Authors
-
Valeria Rudman-Melnick, Mike Adam, Kaitlynn Stowers, Andrew Potter, Qing Ma, Saagar M. Chokshi, Davy Vanhoutte, Íñigo Valiente-Alandí, Diana M. Lindquist, Michelle L. Nieman, Matthew Kofron, Eunah Chung, Joo‐Seop Park, S. Steven Potter, Prasad DevarajanList of authors in order
- Landing page
-
https://doi.org/10.1038/s41598-023-50195-0Publisher landing page
- PDF URL
-
https://www.nature.com/articles/s41598-023-50195-0.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.nature.com/articles/s41598-023-50195-0.pdfDirect OA link when available
- Concepts
-
Kidney, Kidney disease, Fibrosis, Biology, Acute kidney injury, Stromal cell, Nephron, Fibroblast, Kidney development, Fibroblast growth factor 23, Pathology, Cancer research, Cell biology, Medicine, Internal medicine, Embryonic stem cell, Endocrinology, Gene, Parathyroid hormone, Cell culture, Genetics, CalciumTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
18Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 11, 2024: 6, 2023: 1Per-year citation counts (last 5 years)
- References (count)
-
73Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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