A single-cell multiomic analysis of kidney organoid differentiation

被引：26

作者：

Yoshimura, Yasuhiro ^{[1
]}

Muto, Yoshiharu ^{[1
]}

Ledru, Nicolas ^{[1
]}

Wu, Haojia ^{[1
]}

Omachi, Kohei ^{[1
]}

Miner, Jeffrey H. ^{[1
]}

Humphreys, Benjamin D. ^{[1
,2
]}

机构：

[1] Washington Univ St Louis, Sch Med, Dept Med, Div Nephrol, St Louis, MO 63110 USA

[2] Washington Univ St Louis, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2023年 / 120卷 / 20期

基金：

日本学术振兴会;

关键词：

kidney organoid; scRNA-seq; scATAC-seq; CUT & RUN; CRISPR interference; PLURIPOTENT STEM-CELLS; GENE-EXPRESSION; PODOCYTE; REVEALS; SEGMENTATION; PROGENITORS; GENERATION; MAFB;

D O I：

10.1073/pnas.2219699120

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Kidney organoids differentiated from pluripotent stem cells are powerful models of kidney development and disease but are characterized by cell immaturity and off-target cell fates. Comparing the cell-specific gene regulatory landscape during organoid differentiation with human adult kidney can serve to benchmark progress in differentiation at the epigenome and transcriptome level for individual organoid cell types. Using single-cell multiome and histone modification analysis, we report more broadly open chromatin in organoid cell types compared to the human adult kidney. We infer enhancer dynamics by cis-coaccessibility analysis and validate an enhancer driving transcription of HNF1B by CRISPR interference both in cultured proximal tubule cells and also during organoid differentiation. Our approach provides an experimental framework to judge the cell-specific maturation state of human kidney organoids and shows that kidney organoids can be used to validate individual gene regulatory networks that regulate differentiation.

引用

页数：10

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