IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45752-8.html
   My bibliography  Save this article

High resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing

Author

Listed:
  • Haojia Wu

    (Department of Medicine, Washington University in St. Louis School of Medicine)

  • Eryn E. Dixon

    (Department of Medicine, Washington University in St. Louis School of Medicine)

  • Qiao Xuanyuan

    (Department of Medicine, Washington University in St. Louis School of Medicine)

  • Juanru Guo

    (Department of Medicine, Washington University in St. Louis School of Medicine)

  • Yasuhiro Yoshimura

    (Department of Medicine, Washington University in St. Louis School of Medicine)

  • Chitnis Debashish

    (10X Genomics)

  • Anezka Niesnerova

    (10X Genomics)

  • Hao Xu

    (10X Genomics
    Aplex Bio AB)

  • Morgane Rouault

    (10X Genomics)

  • Benjamin D. Humphreys

    (Department of Medicine, Washington University in St. Louis School of Medicine
    Washington University in St. Louis School of Medicine)

Abstract

Emerging spatially resolved transcriptomics technologies allow for the measurement of gene expression in situ at cellular resolution. We apply direct RNA hybridization-based in situ sequencing (dRNA HybISS, Cartana part of 10xGenomics) to compare male and female healthy mouse kidneys and the male kidney injury and repair timecourse. A pre-selected panel of 200 genes is used to identify cell state dynamics patterns during injury and repair. We develop a new computational pipeline, CellScopes, for the rapid analysis, multi-omic integration and visualization of spatially resolved transcriptomic datasets. The resulting dataset allows us to resolve 13 kidney cell types within distinct kidney niches, dynamic alterations in cell state over the course of injury and repair and cell-cell interactions between leukocytes and kidney parenchyma. At late timepoints after injury, C3+ leukocytes are enriched near pro-inflammatory, failed-repair proximal tubule cells. Integration of snRNA-seq dataset from the same injury and repair samples also allows us to impute the spatial localization of genes not directly measured by dRNA HybISS.

Suggested Citation

  • Haojia Wu & Eryn E. Dixon & Qiao Xuanyuan & Juanru Guo & Yasuhiro Yoshimura & Chitnis Debashish & Anezka Niesnerova & Hao Xu & Morgane Rouault & Benjamin D. Humphreys, 2024. "High resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45752-8
    DOI: 10.1038/s41467-024-45752-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45752-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-45752-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Michael S. Balzer & Tomohito Doke & Ya-Wen Yang & Daniel L. Aldridge & Hailong Hu & Hung Mai & Dhanunjay Mukhi & Ziyuan Ma & Rojesh Shrestha & Matthew B. Palmer & Christopher A. Hunter & Katalin Suszt, 2022. "Single-cell analysis highlights differences in druggable pathways underlying adaptive or fibrotic kidney regeneration," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Blue B. Lake & Song Chen & Masato Hoshi & Nongluk Plongthongkum & Diane Salamon & Amanda Knoten & Anitha Vijayan & Ramakrishna Venkatesh & Eric H. Kim & Derek Gao & Joseph Gaut & Kun Zhang & Sanjay Ja, 2019. "A single-nucleus RNA-sequencing pipeline to decipher the molecular anatomy and pathophysiology of human kidneys," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    3. Parker C. Wilson & Yoshiharu Muto & Haojia Wu & Anil Karihaloo & Sushrut S. Waikar & Benjamin D. Humphreys, 2022. "Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    4. Zhen Miao & Michael S. Balzer & Ziyuan Ma & Hongbo Liu & Junnan Wu & Rojesh Shrestha & Tamas Aranyi & Amy Kwan & Ayano Kondo & Marco Pontoglio & Junhyong Kim & Mingyao Li & Klaus H. Kaestner & Katalin, 2021. "Single cell regulatory landscape of the mouse kidney highlights cellular differentiation programs and disease targets," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    5. Brendan F. Miller & Feiyang Huang & Lyla Atta & Arpan Sahoo & Jean Fan, 2022. "Reference-free cell type deconvolution of multi-cellular pixel-resolution spatially resolved transcriptomics data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    6. Yoshiharu Muto & Eryn E. Dixon & Yasuhiro Yoshimura & Haojia Wu & Kohei Omachi & Nicolas Ledru & Parker C. Wilson & Andrew J. King & N. Eric Olson & Marvin G. Gunawan & Jay J. Kuo & Jennifer H. Cox & , 2022. "Defining cellular complexity in human autosomal dominant polycystic kidney disease by multimodal single cell analysis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    7. Christoph Kuppe & Mahmoud M. Ibrahim & Jennifer Kranz & Xiaoting Zhang & Susanne Ziegler & Javier Perales-Patón & Jitske Jansen & Katharina C. Reimer & James R. Smith & Ross Dobie & John R. Wilson-Kan, 2021. "Decoding myofibroblast origins in human kidney fibrosis," Nature, Nature, vol. 589(7841), pages 281-286, January.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Nicolas Ledru & Parker C. Wilson & Yoshiharu Muto & Yasuhiro Yoshimura & Haojia Wu & Dian Li & Amish Asthana & Stefan G. Tullius & Sushrut S. Waikar & Giuseppe Orlando & Benjamin D. Humphreys, 2024. "Predicting proximal tubule failed repair drivers through regularized regression analysis of single cell multiomic sequencing," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Wei E. Gordon & Seungbyn Baek & Hai P. Nguyen & Yien-Ming Kuo & Rachael Bradley & Sarah L. Fong & Nayeon Kim & Alex Galazyuk & Insuk Lee & Melissa R. Ingala & Nancy B. Simmons & Tony Schountz & Lisa N, 2024. "Integrative single-cell characterization of a frugivorous and an insectivorous bat kidney and pancreas," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    3. Yoshiharu Muto & Eryn E. Dixon & Yasuhiro Yoshimura & Haojia Wu & Kohei Omachi & Nicolas Ledru & Parker C. Wilson & Andrew J. King & N. Eric Olson & Marvin G. Gunawan & Jay J. Kuo & Jennifer H. Cox & , 2022. "Defining cellular complexity in human autosomal dominant polycystic kidney disease by multimodal single cell analysis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Nehaben A. Gujarati & Bismark O. Frimpong & Malaika Zaidi & Robert Bronstein & Monica P. Revelo & John D. Haley & Igor Kravets & Yiqing Guo & Sandeep K. Mallipattu, 2024. "Podocyte-specific KLF6 primes proximal tubule CaMK1D signaling to attenuate diabetic kidney disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    5. Urban Lendahl & Lars Muhl & Christer Betsholtz, 2022. "Identification, discrimination and heterogeneity of fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. Shirong Cao & Yu Pan & Andrew S. Terker & Juan Pablo Arroyo Ornelas & Yinqiu Wang & Jiaqi Tang & Aolei Niu & Sarah Abu Kar & Mengdi Jiang & Wentian Luo & Xinyu Dong & Xiaofeng Fan & Suwan Wang & Matth, 2023. "Epidermal growth factor receptor activation is essential for kidney fibrosis development," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Li-Kai Chu & Xu Cao & Lin Wan & Qiang Diao & Yu Zhu & Yu Kan & Li-Li Ye & Yi-Ming Mao & Xing-Qiang Dong & Qian-Wei Xiong & Ming-Cui Fu & Ting Zhang & Hui-Ting Zhou & Shi-Zhong Cai & Zhou-Rui Ma & Ssu-, 2023. "Autophagy of OTUD5 destabilizes GPX4 to confer ferroptosis-dependent kidney injury," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. LiangYu Zhao & Sha Han & HengChuan Su & JianYing Li & ErLei Zhi & Peng Li & ChenCheng Yao & RuHui Tian & HuiXing Chen & HuiRong Chen & JiaQiang Luo & ChenKun Shi & ZhiYong Ji & JianLin Hu & Gang Wu & , 2022. "Single-cell transcriptome atlas of the human corpus cavernosum," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    9. Marie Bobowski-Gerard & Clémence Boulet & Francesco P. Zummo & Julie Dubois-Chevalier & Céline Gheeraert & Mohamed Bou Saleh & Jean-Marc Strub & Amaury Farce & Maheul Ploton & Loïc Guille & Jimmy Vand, 2022. "Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    10. Baptiste Lamarthée & Jasper Callemeyn & Yannick Van Herck & Asier Antoranz & Dany Anglicheau & Patrick Boada & Jan Ulrich Becker & Tim Debyser & Frederik De Smet & Katrien De Vusser & Maëva Eloudzeri , 2023. "Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    11. Naomi Pode-Shakked & Megan Slack & Nambirajan Sundaram & Ruth Schreiber & Kyle W. McCracken & Benjamin Dekel & Michael Helmrath & Raphael Kopan, 2023. "RAAS-deficient organoids indicate delayed angiogenesis as a possible cause for autosomal recessive renal tubular dysgenesis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    12. Haoyang Li & Juexiao Zhou & Zhongxiao Li & Siyuan Chen & Xingyu Liao & Bin Zhang & Ruochi Zhang & Yu Wang & Shiwei Sun & Xin Gao, 2023. "A comprehensive benchmarking with practical guidelines for cellular deconvolution of spatial transcriptomics," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    13. Merve Kayhan & Judith Vouillamoz & Daymé Gonzalez Rodriguez & Milica Bugarski & Yasutaka Mitamura & Julia Gschwend & Christoph Schneider & Andrew Hall & David Legouis & Cezmi A. Akdis & Leary Peter & , 2023. "Intrinsic TGF-β signaling attenuates proximal tubule mitochondrial injury and inflammation in chronic kidney disease," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    14. Kalen Clifton & Manjari Anant & Gohta Aihara & Lyla Atta & Osagie K. Aimiuwu & Justus M. Kebschull & Michael I. Miller & Daniel Tward & Jean Fan, 2023. "STalign: Alignment of spatial transcriptomics data using diffeomorphic metric mapping," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    15. Bujamin H. Vokshi & Guillaume Davidson & Nassim Tawanaie Pour Sedehi & Alexandra Helleux & Marc Rippinger & Alexandre R. Haller & Justine Gantzer & Jonathan Thouvenin & Philippe Baltzinger & Rachida B, 2023. "SMARCB1 regulates a TFCP2L1-MYC transcriptional switch promoting renal medullary carcinoma transformation and ferroptosis resistance," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    16. Michael S. Balzer & Tomohito Doke & Ya-Wen Yang & Daniel L. Aldridge & Hailong Hu & Hung Mai & Dhanunjay Mukhi & Ziyuan Ma & Rojesh Shrestha & Matthew B. Palmer & Christopher A. Hunter & Katalin Suszt, 2022. "Single-cell analysis highlights differences in druggable pathways underlying adaptive or fibrotic kidney regeneration," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    17. Fei Wang & Peiwen Ding & Xue Liang & Xiangning Ding & Camilla Blunk Brandt & Evelina Sjöstedt & Jiacheng Zhu & Saga Bolund & Lijing Zhang & Laura P. M. H. Rooij & Lihua Luo & Yanan Wei & Wandong Zhao , 2022. "Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    18. Michal Polonsky & Louisa M. S. Gerhardt & Jina Yun & Kari Koppitch & Katsuya Lex Colón & Henry Amrhein & Barbara Wold & Shiwei Zheng & Guo-Cheng Yuan & Matt Thomson & Long Cai & Andrew P. McMahon, 2024. "Spatial transcriptomics defines injury specific microenvironments and cellular interactions in kidney regeneration and disease," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    19. Victor Hugo Canela & William S. Bowen & Ricardo Melo Ferreira & Farooq Syed & James E. Lingeman & Angela R. Sabo & Daria Barwinska & Seth Winfree & Blue B. Lake & Ying-Hua Cheng & Joseph P. Gaut & Mic, 2023. "A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    20. Camille Cohen & Rana Mhaidly & Hugo Croizer & Yann Kieffer & Renaud Leclere & Anne Vincent-Salomon & Catherine Robley & Dany Anglicheau & Marion Rabant & Aurélie Sannier & Marc-Olivier Timsit & Sean E, 2024. "WNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45752-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.