Stable iPSC-derived NKX2-1+ lung bud tip progenitor organoids give rise to airway and alveolar cell types.
Bud tip progenitor
Human pluripotent stem cell
Lung organoid
Single cell RNA sequencing
Journal
Development (Cambridge, England)
ISSN: 1477-9129
Titre abrégé: Development
Pays: England
ID NLM: 8701744
Informations de publication
Date de publication:
15 10 2022
15 10 2022
Historique:
received:
28
02
2022
accepted:
28
07
2022
entrez:
30
8
2022
pubmed:
31
8
2022
medline:
1
9
2022
Statut:
ppublish
Résumé
Bud tip progenitors (BTPs) in the developing lung give rise to all epithelial cell types found in the airways and alveoli. This work aimed to develop an iPSC organoid model enriched with NKX2-1+ BTP-like cells. Building on previous studies, we optimized a directed differentiation paradigm to generate spheroids with more robust NKX2-1 expression. Spheroids were expanded into organoids that possessed NKX2-1+/CPM+ BTP-like cells, which increased in number over time. Single cell RNA-sequencing analysis revealed a high degree of transcriptional similarity between induced BTPs (iBTPs) and in vivo BTPs. Using FACS, iBTPs were purified and expanded as induced bud tip progenitor organoids (iBTOs), which maintained an enriched population of bud tip progenitors. When iBTOs were directed to differentiate into airway or alveolar cell types using well-established methods, they gave rise to organoids composed of organized airway or alveolar epithelium, respectively. Collectively, iBTOs are transcriptionally and functionally similar to in vivo BTPs, providing an important model for studying human lung development and differentiation.
Identifiants
pubmed: 36039869
pii: 276470
doi: 10.1242/dev.200693
pmc: PMC9534489
pii:
doi:
Substances chimiques
NKX2-1 protein, human
0
Thyroid Nuclear Factor 1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM145470
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM145304
Pays : United States
Organisme : NHLBI NIH HHS
ID : F30 HL156474
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL152531
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL119215
Pays : United States
Organisme : NIDCR NIH HHS
ID : T32 DE007057
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007863
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL146162
Pays : United States
Informations de copyright
© 2022. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests J.R.S. holds intellectual property rights pertaining to lung organoid technologies.
Références
J Biol. 2004;3(3):11
pubmed: 15186480
Stem Cell Reports. 2014 Sep 9;3(3):394-403
pubmed: 25241738
Stem Cell Reports. 2018 May 8;10(5):1579-1595
pubmed: 29657097
J Clin Invest. 2017 Jun 1;127(6):2277-2294
pubmed: 28463226
Stem Cell Reports. 2016 Nov 8;7(5):826-839
pubmed: 27720905
Stem Cell Reports. 2018 Jan 9;10(1):101-119
pubmed: 29249664
Elife. 2021 Oct 06;10:
pubmed: 34612202
Nat Biotechnol. 2006 Nov;24(11):1392-401
pubmed: 17053790
Cell Stem Cell. 2017 Oct 5;21(4):472-488.e10
pubmed: 28965766
Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16806-11
pubmed: 17077151
Dev Biol. 2005 Jul 1;283(1):226-39
pubmed: 15907834
Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20545-20555
pubmed: 31548395
Dev Biol. 2018 Feb 1;434(1):121-132
pubmed: 29217200
Elife. 2022 Apr 08;11:
pubmed: 35394424
Commun Biol. 2021 May 20;4(1):601
pubmed: 34017045
Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4449-54
pubmed: 17360544
Dev Cell. 2022 Jul 11;57(13):1598-1614.e8
pubmed: 35679862
Cell Rep. 2016 Jun 28;16(1):66-78
pubmed: 27320915
Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15348-53
pubmed: 22949635
iScience. 2020 May 22;23(5):101083
pubmed: 32380423
Am J Physiol Lung Cell Mol Physiol. 2018 Dec 1;315(6):L921-L932
pubmed: 30211653
Dev Cell. 2009 Jul;17(1):62-74
pubmed: 19619492
Cell Stem Cell. 2014 Feb 6;14(2):237-52
pubmed: 24412311
Cell Stem Cell. 2021 Jan 7;28(1):79-95.e8
pubmed: 33098807
Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16287-92
pubmed: 19805295
Front Cell Dev Biol. 2020 Jul 21;8:574
pubmed: 32850782
Elife. 2020 Jun 09;9:
pubmed: 32515350
Nat Cell Biol. 2017 May;19(5):542-549
pubmed: 28436965
Genome Biol. 2019 Dec 23;20(1):296
pubmed: 31870423
Curr Pathobiol Rep. 2017;5(2):223-231
pubmed: 28596933
Cell. 2021 Jun 24;184(13):3573-3587.e29
pubmed: 34062119
Stem Cell Res. 2013 Nov;11(3):1003-12
pubmed: 23917481
Stem Cell Reports. 2016 Jan 12;6(1):18-25
pubmed: 26724905
Elife. 2019 Mar 04;8:
pubmed: 30829572
Dev Biol. 2016 Aug 15;416(2):338-46
pubmed: 27341756
Development. 2004 Apr;131(7):1651-62
pubmed: 14998924
Development. 2017 Nov 1;144(21):3879-3893
pubmed: 28947536
Nat Protoc. 2011 Nov 10;6(12):1920-8
pubmed: 22082986
Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):E4456-64
pubmed: 24191021
Nat Med. 2021 May;27(5):806-814
pubmed: 33958799
Dev Biol. 1999 May 1;209(1):60-71
pubmed: 10208743
Cell Stem Cell. 2017 Jun 1;20(6):844-857.e6
pubmed: 28366587
Cell. 2021 Jun 10;184(12):3281-3298.e22
pubmed: 34019796
Exp Cell Res. 2005 Jun 10;306(2):357-63
pubmed: 15925592
Nature. 2017 May 11;545(7653):238-242
pubmed: 28467820
Nat Biotechnol. 2018 Dec 03;:
pubmed: 30531897
Nature. 2014 Dec 18;516(7531):400-4
pubmed: 25363776
Genesis. 2005 Jan;41(1):23-32
pubmed: 15645446
Cell Stem Cell. 2012 Apr 6;10(4):385-97
pubmed: 22482504
Nat Biotechnol. 2014 Jan;32(1):84-91
pubmed: 24291815
Nat Methods. 2017 Nov;14(11):1097-1106
pubmed: 28967890
Nat Commun. 2020 Aug 27;11(1):4158
pubmed: 32855417
Development. 1991 Dec;113(4):1093-104
pubmed: 1811929
Dev Dyn. 2009 Aug;238(8):1999-2013
pubmed: 19618463
Dev Cell. 2009 Aug;17(2):290-8
pubmed: 19686689
Elife. 2016 Sep 28;5:
pubmed: 27677847
Curr Protoc Stem Cell Biol. 2020 Sep;54(1):e118
pubmed: 32640120
Nat Protoc. 2019 Dec;14(12):3303-3332
pubmed: 31732721
Nature. 2018 Jun;558(7708):132-135
pubmed: 29795348
Nat Biotechnol. 2011 Mar;29(3):267-72
pubmed: 21358635
Methods Cell Biol. 2020;159:115-141
pubmed: 32586440
Elife. 2017 Jun 30;6:
pubmed: 28665271
Nat Commun. 2014 May 29;5:3923
pubmed: 24879355
Stem Cells. 2016 Nov;34(11):2635-2647
pubmed: 27299363
Development. 2007 Jul;134(13):2521-31
pubmed: 17522155
Dev Biol. 2012 Sep 1;369(1):54-64
pubmed: 22750256
Dev Cell. 2020 Aug 24;54(4):516-528.e7
pubmed: 32841595
Dev Cell. 2020 Apr 6;53(1):117-128.e6
pubmed: 32109386
Am J Stem Cells. 2013 Jun 30;2(2):119-31
pubmed: 23862100
Development. 2009 Nov;136(22):3741-5
pubmed: 19855016
Dev Biol. 1995 Dec;172(2):694-8
pubmed: 8612983
Stem Cell Reports. 2015 Apr 14;4(4):569-77
pubmed: 25772471
Sci Rep. 2019 Mar 26;9(1):5233
pubmed: 30914743
Development. 2019 Jan 22;146(2):
pubmed: 30578291
Nat Protoc. 2019 Feb;14(2):518-540
pubmed: 30664680
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Differentiation. 2016 Dec;92(5):281-290
pubmed: 27087651
Bioessays. 2020 Jun;42(6):e2000006
pubmed: 32310312
Gastroenterology. 2007 Aug;133(2):710-2
pubmed: 17681188
Dev Dyn. 2015 Mar;244(3):342-66
pubmed: 25470458
Development. 2007 May;134(10):1991-2000
pubmed: 17428829
Cell Stem Cell. 2020 Apr 2;26(4):593-608.e8
pubmed: 32004478
Development. 2011 Mar;138(5):971-81
pubmed: 21303850
Elife. 2015 Mar 24;4:
pubmed: 25803487
Nature. 2011 Feb 3;470(7332):105-9
pubmed: 21151107
Development. 1994 Aug;120(8):2153-61
pubmed: 7523056