Building a reference tissue atlas for the human kidney

Building a reference tissue atlas for the human kidney

March 14, 2022

In a collaborative effort, several investigators across the Kidney Precision Medicine Project (KPMP) consortium have detailed the first steps toward building a reference tissue atlas for the human kidney. This pre-print is available in bioRxiv. The goals of KPMP are to ethically obtain and evaluate kidney biopsies from participants with AKI, CKD or reference groups; to define disease subgroups; to identify critical cells, pathways, and targets for novel therapies; and to create a kidney tissue atlas.

This pre-print focuses on the latter goal of creating a kidney tissue atlas. The manuscript describes KPMP's efforts towards building a spatially-specified human tissue atlas at the single-cell resolution with molecular details of the kidney in health and disease. It describes 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.  KPMP investigators used 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.

Matthias Kretzler, co-Principal Investigator at the KPMP Central Hub states "This is a critical step towards the goal of KPMP to define the molecular processes of kidney function and failure in AKI and CKD. The study not only establishes cell reference states from multiple molecular view points, but also provides a road map how to integrate highly diverse data sets from a common tissue source."

This pre-print is now in press at Science Advances.