RT Journal Article
SR Electronic
T1 Comprehensive single cell RNAseq analysis of the kidney reveals novel cell types and unexpected cell plasticity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 203125
DO 10.1101/203125
A1 Jihwan Park
A1 Rojesh Shrestha
A1 Chengxiang Qiu
A1 Ayano Kondo
A1 Shizheng Huang
A1 Max Werth
A1 Mingyao Li
A1 Jonathan Barasch
A1 Katalin Suszták
YR 2017
UL http://biorxiv.org/content/early/2017/10/13/203125.abstract
AB A key limitations to understand kidney function and disease development has been that specific cell types responsible for specific homeostatic kidney function or disease phenotypes have not been defined at the molecular level.To fill this gap, we characterized 57,979 cells from healthy mouse kidneys using unbiased single-cell RNA sequencing. We show that genetic mutations that present with similar phenotypes mostly affect genes that are expressed in a single unique differentiated cell type. On the other hand, we found unexpected cell plasticity of epithelial cells in the final segment of the kidney (collecting duct) that is responsible for final composition of the urine. Using computational cell trajectory analysis and in vivo linage tracing, we found that, intercalated cells (that secrete protons) and principal cells (that maintain salt, water and potassium balance) undergo a Notch mediated interconversion via a newly identified transitional cell type. In disease states this transition is shifted towards the principal cell fate. Loss of intercalated cells likely contributes to metabolic acidosis observed in kidney disease.In summary, single cell analysis advanced a mechanistic description of kidney diseases by identifying a defective homeostatic cell lineage.One Sentence Summary A comprehensive single cell atlas of the kidney reveals a transitional cell type and cell plasticity determined by Notch signaling which is defective in chronic kidney disease.