A reference tissue atlas for the human kidney

Autor: Tarek M. El-Achkar, Rajasree Menon, Annapurna Pamreddy, Jeffrey B. Hodgin, Brad H. Rovin, Becky Steck, Seth Winfree, Abhijit S. Naik, Yongqun He, Kumar Sharma, Michael Rose, John P. Shapiro, Evren U. Azeloglu, Kun Zhang, Samir M. Parikh, Zoltan Laszik, Blue B. Lake, Tara K. Sigdel, Theodore Alexandrov, Sanjay Jain, Guanshi Zhang, Ian H. de Boer, Edgar A. Otto, Jonathan Himmelfarb, Jens Hansen, Priyanka Rashmi, M. Todd Valerius, Rachel Sealfon, Daria Barwinska, John Cijiang He, Ravi Iyengar, Olga G. Troyanskaya, Laura Barisoni, Pierre C. Dagher, Minnie M. Sarwal, Matthias Kretzler, Lisa M. Satlin, Dejan Dobi, Christopher R. Anderton, Michael T. Eadon, Dušan Veličković
Rok vydání: 2020
Předmět:
DOI: 10.1101/2020.07.23.216507
Popis: Kidney Precision Medicine Project (KPMP) is building a spatially-specified human tissue atlas at the single-cell resolution with molecular details of the kidney in health and disease. Here, we describe the construction of an integrated reference tissue map of cells, pathways and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 55 subjects. We use single-cell and -nucleus transcriptomics, subsegmental laser microdissection bulk transcriptomics and proteomics, near-single-cell proteomics, 3-D nondestructive and CODEX imaging, and spatial metabolomics data to hierarchically identify genes, pathways and cells. Integrated data from these different technologies coherently describe cell types/subtypes within different nephron segments and interstitium. These spatial profiles identify cell-level functional organization of the kidney tissue as indicative of their physiological functions and map different cell subtypes to genes, proteins, metabolites and pathways. Comparison of transcellular sodium reabsorption along the nephron to levels of mRNAs encoding the different sodium transporter genes indicate that mRNA levels are largely congruent with physiological activity.This reference atlas provides an initial framework for molecular classification of kidney disease when multiple molecular mechanisms underlie convergent clinical phenotypes.
Databáze: OpenAIRE