Evaluation of variability in human kidney organoids

被引：185

作者：

Phipson, Belinda ^{[1
]}

Er, Pei X. ^{[1
]}

Combes, Alexander N. ^{[1
,2
]}

Forbes, Thomas A. ^{[1
,3
,4
]}

Howden, Sara E. ^{[1
,2
]}

Zappia, Luke ^{[1
,5
]}

Yen, Hsan-Jan ^{[1
]}

Lawlor, Kynan T. ^{[1
]}

Hale, Lorna J. ^{[1
,4
]}

Sun, Jane ^{[6
]}

Wolvetang, Ernst ^{[6
]}

Takasato, Minoru ^{[1
,7
]}

Oshlack, Alicia ^{[1
,5
]}

Little, Melissa H. ^{[1
,2
,4
]}

机构：

[1] Murdoch Childrens Res Inst, Melbourne, Vic, Australia

[2] Univ Melbourne, Dept Anat & Neurosci, Melbourne, Vic, Australia

[3] Royal Childrens Hosp, Dept Nephrol, Melbourne, Vic, Australia

[4] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia

[5] Univ Melbourne, Sch Biosci, Melbourne, Vic, Australia

[6] Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld, Australia

[7] RIKEN, Ctr Biosyst Dynam Res, Kobe, Hyogo, Japan

来源：

NATURE METHODS | 2019年 / 16卷 / 01期

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

PLURIPOTENT STEM-CELLS; MODELING HUMAN-DEVELOPMENT; SELF-FORMATION; FEATURES; DISEASE; GENES; MOUSE;

D O I：

10.1038/s41592-018-0253-2

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

The utility of human pluripotent stem cell-derived kidney organoids relies implicitly on the robustness and transferability of the protocol. Here we analyze the sources of transcriptional variation in a specific kidney organoid protocol. Although individual organoids within a differentiation batch showed strong transcriptional correlation, we noted significant variation between experimental batches, particularly in genes associated with temporal maturation. Single-cell profiling revealed shifts in nephron patterning and proportions of component cells. Distinct induced pluripotent stem cell clones showed congruent transcriptional programs, with interexperimental and interclonal variation also strongly associated with nephron patterning. Epithelial cells isolated from organoids aligned with total organoids at the same day of differentiation, again implicating relative maturation as a confounder. This understanding of experimental variation facilitated an optimized analysis of organoid-based disease modeling, thereby increasing the utility of kidney organoids for personalized medicine and functional genomics.

引用

页码：79 / +

页数：11

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