دورية أكاديمية
أعرض في EDS

Multi-omics profiling of mouse polycystic kidney disease progression at a single cell resolution.

التفاصيل البيبلوغرافية
العنوان: Multi-omics profiling of mouse polycystic kidney disease progression at a single cell resolution.
المؤلفون: Muto Y; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Yoshimura Y; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Wu H; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Chang-Panesso M; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Ledru N; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Woodward OM; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA., Outeda P; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA., Cheng T; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Mahjoub MR; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.; Department of Cell Biology and Physiology, Washington University in St. Louis, St. Louis, MO, USA., Watnick TJ; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA., Humphreys BD; Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.; Department of Developmental Biology, Washington University in St. Louis, St. Louis, MO, USA.
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2024 May 31. Date of Electronic Publication: 2024 May 31.
نوع المنشور: Journal Article; Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and causes significant morbidity, ultimately leading to end-stage kidney disease. PKD pathogenesis is characterized by complex and dynamic alterations in multiple cell types during disease progression, hampering a deeper understanding of disease mechanism and the development of therapeutic approaches. Here, we generate a single nucleus multimodal atlas of an orthologous mouse PKD model at early, mid and late timepoints, consisting of 125,434 single-nucleus transcriptomic and epigenetic multiomes. We catalogue differentially expressed genes and activated epigenetic regions in each cell type during PKD progression, characterizing cell-type-specific responses to Pkd1 deletion. We describe heterogeneous, atypical collecting duct cells as well as proximal tubular cells that constitute cyst epithelia in PKD. The transcriptional regulation of the cyst lining cell marker GPRC5A is conserved between mouse and human PKD cystic epithelia, suggesting shared gene regulatory pathways. Our single nucleus multiomic analysis of mouse PKD provides a foundation to understand the earliest changes molecular deregulation in a mouse model of PKD at a single-cell resolution.
Competing Interests: Competing Interest Statement: B.D.H. is a consultant for Janssen Research & Development, LLC, Pfizer and Chinook Therapeutics, holds equity in Chinook Therapeutics and grant funding from Chinook Therapeutics and Janssen Research & Development, LLC. O.M.W has received grants from AstraZeneca unrelated to the current work. The remaining authors declare no competing interests.
References: Nat Commun. 2018 Aug 6;9(1):3115. (PMID: 30082728)
Cell Rep. 2018 Oct 30;25(5):1304-1317.e5. (PMID: 30380420)
Nature. 2023 Jul;619(7970):585-594. (PMID: 37468583)
Nat Commun. 2022 Oct 30;13(1):6497. (PMID: 36310237)
Am J Physiol Renal Physiol. 2023 Apr 1;324(4):F404-F422. (PMID: 36794754)
J Am Soc Nephrol. 2008 Jul;19(7):1300-10. (PMID: 18385427)
J Clin Invest. 2012 Nov;122(11):4257-73. (PMID: 23064367)
N Engl J Med. 2012 Dec 20;367(25):2407-18. (PMID: 23121377)
Lancet. 2007 Apr 14;369(9569):1287-1301. (PMID: 17434405)
Genes Dev. 2018 Jun 1;32(11-12):781-793. (PMID: 29891559)
Mol Cell. 2018 Sep 6;71(5):858-871.e8. (PMID: 30078726)
J Am Soc Nephrol. 2023 Apr 1;34(4):554-571. (PMID: 36735940)
Nat Commun. 2019 Jun 27;10(1):2832. (PMID: 31249312)
Proc Natl Acad Sci U S A. 2021 Jul 6;118(27):. (PMID: 34183416)
Cancer Invest. 2013 Feb;31(2):103-10. (PMID: 23320791)
Nat Commun. 2021 Apr 13;12(1):2190. (PMID: 33850129)
Science. 1995 Aug 11;269(5225):847-50. (PMID: 7543698)
Signal Transduct Target Ther. 2022 Nov 8;7(1):376. (PMID: 36347846)
Annu Rev Cancer Biol. 2019 Mar;3:203-222. (PMID: 31650096)
J Am Soc Nephrol. 2005 Sep;16(9):2724-31. (PMID: 16049073)
Nat Genet. 2021 Dec;53(12):1649-1663. (PMID: 34635846)
Elife. 2021 Jul 19;10:. (PMID: 34279220)
Nat Commun. 2024 Jan 9;15(1):406. (PMID: 38195686)
Genome Biol. 2020 Jun 2;21(1):130. (PMID: 32487174)
Nat Methods. 2017 Oct;14(10):979-982. (PMID: 28825705)
Nat Methods. 2019 Dec;16(12):1289-1296. (PMID: 31740819)
Cell. 2021 Jun 24;184(13):3573-3587.e29. (PMID: 34062119)
Science. 2018 May 18;360(6390):758-763. (PMID: 29622724)
Biomed Res Int. 2018 Oct 17;2018:1823726. (PMID: 30417009)
Nat Commun. 2022 Sep 6;13(1):5253. (PMID: 36068241)
Nat Med. 2008 Sep;14(9):979-84. (PMID: 18724376)
Nat Biotechnol. 2018 Jun;36(5):421-427. (PMID: 29608177)
Nat Methods. 2017 Oct;14(10):975-978. (PMID: 28825706)
Kidney Int. 2016 Nov;90(5):1056-1070. (PMID: 27575556)
Genome Res. 2002 Jun;12(6):996-1006. (PMID: 12045153)
Nat Chem Biol. 2023 Oct;19(10):1205-1214. (PMID: 37248411)
Cell Syst. 2019 Apr 24;8(4):329-337.e4. (PMID: 30954475)
Proc Natl Acad Sci U S A. 2020 Jul 7;117(27):15874-15883. (PMID: 32571916)
Kidney Int. 2001 Dec;60(6):2087-96. (PMID: 11737583)
Nat Biotechnol. 2014 Apr;32(4):381-386. (PMID: 24658644)
JCI Insight. 2024 Feb 22;9(4):. (PMID: 38385746)
Development. 2023 Dec 15;150(24):. (PMID: 37982452)
Nature. 2019 Feb;566(7745):496-502. (PMID: 30787437)
Nat Commun. 2017 May 17;8:15206. (PMID: 28513598)
Sci Adv. 2024 Aug 9;10(32):eado2849. (PMID: 39110788)
Nat Rev Nephrol. 2019 Dec;15(12):735-749. (PMID: 31488901)
J Am Soc Nephrol. 2019 Jan;30(1):23-32. (PMID: 30510133)
Science. 2024 Feb 23;383(6685):eadd6371. (PMID: 38386758)
Trends Mol Med. 2014 May;20(5):251-60. (PMID: 24491980)
J Am Soc Nephrol. 2004 Dec;15(12):3035-43. (PMID: 15579506)
Nat Commun. 2019 Sep 26;10(1):4376. (PMID: 31558714)
Nucleic Acids Res. 2022 Jan 7;50(D1):D165-D173. (PMID: 34850907)
معلومات مُعتمدة: R01 DK103740 United States DK NIDDK NIH HHS; U24 DK126110 United States DK NIDDK NIH HHS; U54 DK137332 United States DK NIDDK NIH HHS; UC2 DK126024 United States DK NIDDK NIH HHS
تواريخ الأحداث: Date Created: 20240610 Latest Revision: 20240809
رمز التحديث: 20240809
مُعرف محوري في PubMed: PMC11160654
DOI: 10.1101/2024.05.27.595830
PMID: 38854144
قاعدة البيانات: MEDLINE
الوصف
تدمد:2692-8205
DOI:10.1101/2024.05.27.595830