BACKGROUND: Human kidney organoids hold promise for studying development, disease modelling and drug screening. However, the utility of stem cell-derived kidney tissues will depend on how faithfully these replicate normal fetal development at the level of cellular identity and complexity.
METHODS: Here, we present an integrated analysis of single cell datasets from human kidney organoids and human fetal kidney to assess similarities and differences between the component cell types.
RESULTS: Clusters in the combined dataset contained cells from both organoid and fetal kidney with transcriptional congruence for key stromal, endothelial and nephron cell type-specific markers. Organoid enriched neural, glial and muscle progenitor populations were also evident. Major transcriptional differences between organoid and human tissue were likely related to technical artefacts. Cell type-specific comparisons revealed differences in stromal, endothelial and nephron progenitor cell types including expression of WNT2B in the human fetal kidney stroma.
CONCLUSIONS: This study supports the fidelity of kidney organoids as models of the developing kidney and affirms their potential in disease modelling and drug screening.
Nat Methods. 2019 Jan;16(1):79-87
[PMID:
30573816]
Cell Stem Cell. 2017 Dec 7;21(6):730-746.e6
[PMID:
29129523]
Development. 2017 Oct 1;144(19):3625-3632
[PMID:
28851704]
PLoS One. 2011 Feb 28;6(2):e17286
[PMID:
21386911]
Nat Methods. 2017 Oct;14(10):979-982
[PMID:
28825705]
Dev Biol. 2018 Feb 1;434(1):36-47
[PMID:
29183737]
Development. 1988 Dec;104(4):589-99
[PMID:
3268404]
Development. 2017 Mar 15;144(6):958-962
[PMID:
28292841]
F1000Res. 2016 Aug 31;5:2122
[PMID:
27909575]
Nat Biotechnol. 2014 Apr;32(4):381-386
[PMID:
24658644]
Dev Biol. 2003 Jan 1;253(1):109-24
[PMID:
12490201]
Nat Biotechnol. 2015 Nov;33(11):1193-200
[PMID:
26458176]
BMC Nephrol. 2012 Jul 28;13:70
[PMID:
22839765]
J Am Soc Nephrol. 2018 Mar;29(3):806-824
[PMID:
29449449]
Stem Cell Reports. 2014 Oct 14;3(4):650-62
[PMID:
25358792]
Nat Protoc. 2016 Sep;11(9):1681-92
[PMID:
27560173]
Pediatr Nephrol. 2014 Apr;29(4):695-704
[PMID:
24398540]
Cell Stem Cell. 2014 Jan 2;14(1):53-67
[PMID:
24332837]
Gigascience. 2018 Jul 1;7(7):
[PMID:
30010766]
Cell Stem Cell. 2018 Dec 6;23(6):869-881.e8
[PMID:
30449713]
Nat Protoc. 2014 Oct;9(10):2329-40
[PMID:
25188634]
Nature. 2015 Oct 22;526(7574):564-8
[PMID:
26444236]
Development. 2016 Feb 15;143(4):595-608
[PMID:
26884396]
Dev Cell. 2004 May;6(5):719-28
[PMID:
15130496]
Development. 2014 Jan;141(1):17-27
[PMID:
24284212]
Dev Biol. 2009 Aug 15;332(2):273-86
[PMID:
19501082]
Nat Cell Biol. 2014 Jan;16(1):118-26
[PMID:
24335651]
Dev Cell. 2018 Jun 4;45(5):651-660.e4
[PMID:
29870722]
Genes Dev. 2004 Oct 15;18(20):2431-6
[PMID:
15489289]
Nat Biotechnol. 2018 Jun;36(5):411-420
[PMID:
29608179]
Nat Cell Biol. 2013 Sep;15(9):1035-44
[PMID:
23974041]
Bioinformatics. 2017 Apr 15;33(8):1179-1186
[PMID:
28088763]
Stem Cell Reports. 2018 Aug 14;11(2):470-484
[PMID:
30033089]
Methods. 2015 Sep 1;85:54-61
[PMID:
26142758]
Blood. 2012 May 24;119(21):4823-7
[PMID:
22415753]
Cell. 1996 Sep 20;86(6):897-906
[PMID:
8808625]
Dev Cell. 2014 Apr 28;29(2):188-202
[PMID:
24780737]
Nucleic Acids Res. 2015 Jul 1;43(W1):W589-98
[PMID:
25897122]
Nat Commun. 2015 Oct 23;6:8715
[PMID:
26493500]
Bioinformatics. 2005 Aug 15;21(16):3439-40
[PMID:
16082012]
Science. 2018 Aug 10;361(6402):594-599
[PMID:
30093597]
Nature. 2016 Aug 11;536(7615):238
[PMID:
27120161]
Neural Comput. 2004 Dec;16(12):2639-64
[PMID:
15516276]
Stem Cells. 2013 Mar;31(3):467-78
[PMID:
23225669]
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W305-11
[PMID:
19465376]
Nat Biotechnol. 2015 May;33(5):495-502
[PMID:
25867923]