An atlas of healthy and injured cell states and niches in the human kidney
Blue B. Lake,Rajasree Menon,Seth Winfree,Qiwen Hu,Ricardo Melo Ferreira,Kian Kalhor,Daria Barwinska,Edgar A. Otto,Michael J. Ferkowicz,Dinh Diep,Nongluk Plongthongkum,Amanda Knoten,Sarah Urata,Abhijit S. Naik,Sean Eddy,Bo Zhang,Yan Wu,Diane Salamon,James C. Williams,Xin Wang,Karol S. Balderrama,Paul Hoover,Evan Murray,Anitha Vijayan,Fei Chen,Sushrut S. Waikar,Sylvia E. Rosas,Francis P. Wilson,Paul M. Palevsky,Krzysztof Kiryluk,John R. Sedor,Robert D. Toto,Chirag R. Parikh,Eric H. Kim,Evan Z. Macosko,Peter V. Kharchenko,Joseph P. Gaut,Jeffrey B. Hodgin,Michael T. Eadon,Pierre C. Dagher,Tarek M. El-Achkar,Kun Zhang,Matthias Kretzler,Sanjay Jain +43 more
TLDR
In this paper, a high-resolution cellular atlas of 100 cell types and states, their associated molecular profiles, and interactions within tissue neighborhoods was provided. But, the authors did not identify and define cellular states altered in kidney injury, encompassing cycling, adaptive or maladaptive repair, transitioning and degenerative states affecting several segments.Abstract:
Understanding kidney disease relies upon defining the complexity of cell types and states, their associated molecular profiles, and interactions within tissue neighborhoods. We have applied multiple single-cell or -nucleus assays (>400,000 nuclei/cells) and spatial imaging technologies to a broad spectrum of healthy reference (n = 42) and disease (n = 42) kidneys. This has provided a high resolution cellular atlas of 100 cell types that include rare and novel cell populations. The multi-omic approach provides detailed transcriptomic profiles, epigenomic regulatory factors, and spatial localizations for major cell types spanning the entire kidney. We further identify and define cellular states altered in kidney injury, encompassing cycling, adaptive or maladaptive repair, transitioning and degenerative states affecting several segments. Molecular signatures of these states permitted their localization within injury neighborhoods using spatial transcriptomics, and large-scale 3D imaging analysis of ∼1.2 million neighborhoods provided linkages to active immune responses. These analyses further defined biological pathways relevant to injury niches, including signatures underlying the transition from reference to predicted maladaptive states that were associated with a decline in kidney function during chronic kidney disease. This human kidney cell atlas, including injury cell states and neighborhoods, will be a valuable resource for future studies.read more
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Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function
Gökcen Eraslan,Eugene Drokhlyansky,Shankara Anand,Evgenij Fiškin,Ayshwarya Subramanian,Michal Slyper,Jiali Wang,Nicholas Van Wittenberghe,John M. Rouhana,Julia Waldman,Orr Ashenberg,Monkol Lek,Danielle Dionne,Thet Su Win,Michael S. Cuoco,Olena Kuksenko,Alexander M. Tsankov,Philip A. Branton,Jamie L. Marshall,Anna Greka,Gad Getz,Ayellet V. Segrè,François Aguet,Orit Rozenblatt-Rosen,Kristin G. Ardlie,Aviv Regev +25 more
TL;DR: A framework for multitissue human cell atlases is established and an atlas of 209,126 snRNA-seq profiles from eight tissue types across 16 individuals, archived as frozen tissue as part of the Genotype-Tissue Expression (GTEx) project is generated.
Journal ArticleDOI
The expanding vistas of spatial transcriptomics
TL;DR: The rapidly evolving spatial genomics landscape will enable generalized high-throughput genomic measurements and perturbations to be performed in the context of tissues, which will empower hypothesis generation and biological discovery and bridge the worlds of tissue biology and genomics.
Journal ArticleDOI
Anatomical structures, cell types and biomarkers of the Human Reference Atlas
Katy Börner,Sarah A. Teichmann,Ellen M. Quardokus,James C. Gee,Kristen Browne,David Osumi-Sutherland,Bruce Herr,Andreas Bueckle,Hrishikesh Paul,Muzlifah Haniffa,Laura Jardine,Amy Bernard,Songlin Ding,Jeremy A. Miller,Shin Lin,Marc K. Halushka,Avinash Boppana,Teri A. Longacre,John W. Hickey,Yiing Lin,M. Todd Valerius,Yongqun He,Gloria S. Pryhuber,Xin Sun,Marda Jorgensen,Andrea J. Radtke,Clive Wasserfall,Fiona Ginty,Jonhan Ho,Joel C. Sunshine,Rebecca T. Beuschel,Maigan A. Brusko,Sujin Lee,Rajeev Malhotra,Sanjay Jain,Griffin M. Weber +35 more
TL;DR: The Human Reference Atlas (HRA) aims to map all of the cells of the human body to advance biomedical research and clinical practice as mentioned in this paper, which is the basis for our work.
Journal ArticleDOI
Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury
Christian Hinze,Christine Kocks,Janna Leiz,Nikos Karaiskos,Anastasiya Boltengagen,Shuang Cao,Christopher Mark Skopnik,Jan Klocke,J.H.B. Hardenberg,Helena Stockmann,Inka Gotthardt,Benedikt Obermayer,Laleh Haghverdi,Emanuel Wyler,Markus Landthaler,Sebastian Bachmann,A. Hocker,Victor M. Corman,Jonas Busch,Wolfgang Schneider,Nina Himmerkus,Markus Bleich,Kai-Uwe Eckardt,Philipp Enghard,Nikolaus Rajewsky,Kai M. Schmidt-Ott +25 more
TL;DR: In this article , the cell type-specific transcriptomic responses associated with critical illness-associated acute kidney injury (AKI) in humans have been investigated, highlighting recurrent disease-associated signatures and inter-individual heterogeneity.
Journal ArticleDOI
Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury
Christian Hinze,Christine Kocks,Janna Leiz,Nikos Karaiskos,Anastasiya Boltengagen,Shuang Cao,Christopher Mark Skopnik,Jan Klocke,J.H.B. Hardenberg,Helena Stockmann,Inka Gotthardt,Benedikt Obermayer,Laleh Haghverdi,Emanuel Wyler,Markus Landthaler,Sebastian Bachmann,A. Hocker,Victor M. Corman,Jonas Busch,Wolfgang Schneider,Nina Himmerkus,Markus Bleich,Kai-Uwe Eckardt,Philipp Enghard,Nikolaus Rajewsky,Kai M. Schmidt-Ott +25 more
TL;DR: In this paper , the cell type-specific transcriptomic responses associated with critical illness-associated acute kidney injury (AKI) in humans have been investigated, highlighting recurrent disease-associated signatures and inter-individual heterogeneity.
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