Organoids from human tooth showing epithelial stemness phenotype and differentiation potential.
Ameloblasts
/ cytology
Cell Differentiation
Cells, Cultured
Dental Sac
/ cytology
Epidermal Growth Factor
/ pharmacology
Epithelial Cells
/ cytology
Epithelial-Mesenchymal Transition
/ drug effects
Forkhead Transcription Factors
/ genetics
Humans
Organoids
/ cytology
Phenotype
Receptor, Transforming Growth Factor-beta Type I
/ antagonists & inhibitors
STAT2 Transcription Factor
/ genetics
Single-Cell Analysis
Stem Cells
/ cytology
Transcriptome
Transforming Growth Factor beta
/ metabolism
Ameloblasts
Assembloids
Organoids
Stem cells
TGFβ
Tooth
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
26 Feb 2022
26 Feb 2022
Historique:
received:
07
10
2021
accepted:
01
02
2022
revised:
27
01
2022
entrez:
26
2
2022
pubmed:
27
2
2022
medline:
8
3
2022
Statut:
epublish
Résumé
Insight into human tooth epithelial stem cells and their biology is sparse. Tissue-derived organoid models typically replicate the tissue's epithelial stem cell compartment. Here, we developed a first-in-time epithelial organoid model starting from human tooth. Dental follicle (DF) tissue, isolated from unerupted wisdom teeth, efficiently generated epithelial organoids that were long-term expandable. The organoids displayed a tooth epithelial stemness phenotype similar to the DF's epithelial cell rests of Malassez (ERM), a compartment containing dental epithelial stem cells. Single-cell transcriptomics reinforced this organoid-ERM congruence, and uncovered novel, mouse-mirroring stem cell features. Exposure of the organoids to epidermal growth factor induced transient proliferation and eventual epithelial-mesenchymal transition, highly mimicking events taking place in the ERM in vivo. Moreover, the ERM stemness organoids were able to unfold an ameloblast differentiation process, further enhanced by transforming growth factor-β (TGFβ) and abrogated by TGFβ receptor inhibition, thereby reproducing TGFβ's known key position in amelogenesis. Interestingly, by creating a mesenchymal-epithelial composite organoid (assembloid) model, we demonstrated that the presence of dental mesenchymal cells (i.e. pulp stem cells) triggered ameloblast differentiation in the epithelial stem cells, thus replicating the known importance of mesenchyme-epithelium interaction in tooth development and amelogenesis. Also here, differentiation was abrogated by TGFβ receptor inhibition. Together, we developed novel organoid models empowering the exploration of human tooth epithelial stem cell biology and function as well as their interplay with dental mesenchyme, all at present only poorly defined in humans. Moreover, the new models may pave the way to future tooth-regenerative perspectives.
Identifiants
pubmed: 35217915
doi: 10.1007/s00018-022-04183-8
pii: 10.1007/s00018-022-04183-8
pmc: PMC8881251
doi:
Substances chimiques
Forkhead Transcription Factors
0
STAT2 Transcription Factor
0
Transforming Growth Factor beta
0
mesenchyme fork head 1 protein
0
Epidermal Growth Factor
62229-50-9
Receptor, Transforming Growth Factor-beta Type I
EC 2.7.11.30
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
153Subventions
Organisme : Fonds Wetenschappelijk Onderzoek
ID : 1S84718N
Informations de copyright
© 2022. The Author(s).
Références
Adv Sci (Weinh). 2020 Jul 26;7(18):2001797
pubmed: 32999851
J Dent Res. 2015 Nov;94(11):1591-600
pubmed: 26392003
Prev Chronic Dis. 2011 May;8(3):A50
pubmed: 21477490
J Cell Physiol. 2014 Nov;229(11):1647-59
pubmed: 24610459
Nature. 2015 Nov 19;527(7578):384-8
pubmed: 26550823
Development. 2020 Jan 24;147(2):
pubmed: 31980484
Trends Cancer. 2016 Apr;2(4):176-190
pubmed: 27135056
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 Aug;90(2):218-23
pubmed: 10936841
Development. 2017 May 15;144(10):1775-1786
pubmed: 28442471
Nat Commun. 2020 Sep 23;11(1):4816
pubmed: 32968047
Dev Dyn. 2006 May;235(5):1167-80
pubmed: 16450392
Hum Mol Genet. 2018 Aug 1;27(R2):R99-R107
pubmed: 29796608
J Physiol. 2017 May 15;595(10):3015-3039
pubmed: 27510811
Nature. 2009 May 14;459(7244):262-5
pubmed: 19329995
Sci Rep. 2018 Mar 13;8(1):4450
pubmed: 29535349
Stem Cells Dev. 2012 Jul 20;21(11):2012-25
pubmed: 22122577
J Oral Maxillofac Pathol. 2012 Sep;16(3):395-9
pubmed: 23248473
Proc Natl Acad Sci U S A. 2021 Jun 22;118(25):
pubmed: 34161279
Sci Rep. 2020 Mar 18;10(1):4963
pubmed: 32188889
BMC Genomics. 2015 Aug 12;16:592
pubmed: 26265206
Sci Rep. 2016 Sep 16;6:33644
pubmed: 27633089
J Oral Pathol Med. 1990 Feb;19(2):89-93
pubmed: 2341976
Front Physiol. 2017 Jun 26;8:435
pubmed: 28694781
J Gene Med. 2005 Oct;7(10):1299-310
pubmed: 15906396
Sci Rep. 2019 Jan 23;9(1):368
pubmed: 30675004
Arch Oral Biol. 1996 Dec;41(12):1149-60
pubmed: 9134104
J Endocrinol. 2019 Feb 1;240(2):287-308
pubmed: 30475227
Nat Genet. 1996 Aug;13(4):417-21
pubmed: 8696335
Science. 2021 Feb 19;371(6531):839-846
pubmed: 33602855
J Am Dent Assoc. 2006 Oct;137 Suppl:14S-20S; quiz 38S
pubmed: 17012731
J Exp Zool B Mol Dev Evol. 2009 Jul 15;312B(5):458-64
pubmed: 19205028
Cell Tissue Res. 2013 Jul;353(1):65-78
pubmed: 23715720
Nat Methods. 2017 Nov;14(11):1083-1086
pubmed: 28991892
J Dent Res. 2021 May;100(5):454-463
pubmed: 33478323
Eur J Hum Genet. 2016 Jan;25(1):94-99
pubmed: 27827380
Oral Dis. 2003 Jan;9(1):1-6
pubmed: 12617250
J Dent Res. 2015 Jan;94(1):101-11
pubmed: 25398365
J Anat. 1993 Apr;182 ( Pt 2):153-62
pubmed: 8376190
Annu Rev Pathol. 2020 Jan 24;15:211-234
pubmed: 31550983
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Int J Dev Biol. 2015;59(10-12):471-8
pubmed: 26864488
Cold Spring Harb Perspect Biol. 2012 Apr 01;4(4):a008425
pubmed: 22415375
Arch Oral Biol. 2005 May;50(5):527-32
pubmed: 15777534
Dev Biol. 2008 Jan 15;313(2):887-96
pubmed: 18082678
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Nat Methods. 2007 Mar;4(3):227-30
pubmed: 17322892
Front Physiol. 2019 Mar 12;10:249
pubmed: 30914971
Eur J Oral Sci. 2006 May;114 Suppl 1:154-8; discussion 164-5, 380-1
pubmed: 16674678
Bull Tokyo Dent Coll. 2011;52(4):173-82
pubmed: 22293587
Genome Biol. 2018 Mar 14;19(1):31
pubmed: 29540203
J Biol Chem. 2008 Nov 28;283(48):33658-64
pubmed: 18806264
Dev Dyn. 2003 Sep;228(1):105-12
pubmed: 12950084
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996 Jun;81(6):703-9
pubmed: 8784903
Nucleic Acids Res. 2019 Jan 8;47(D1):D607-D613
pubmed: 30476243
Am J Orthod Dentofacial Orthop. 2000 Aug;118(2):210-9
pubmed: 10935963
J Dent Res. 2008 Aug;87(8):745-50
pubmed: 18650546
Development. 2018 Jun 26;145(12):
pubmed: 29777011
Oral Dis. 2019 Nov;25(8):2010-2019
pubmed: 31529555
Mol Cells. 2011 Apr;31(4):355-60
pubmed: 21359676
Pediatr Dev Pathol. 2008 May-Jun;11(3):206-12
pubmed: 18078367
J Dent Res. 2002 Oct;81(10):695-700
pubmed: 12351668
J Steroid Biochem Mol Biol. 2018 Jun;180:65-72
pubmed: 29341890
Nat Commun. 2020 Oct 19;11(1):5275
pubmed: 33077725
Development. 2018 Jan 8;145(1):
pubmed: 29180573
Biomed Pharmacother. 2019 Oct;118:109235
pubmed: 31336344
Cells. 2020 Jan 28;9(2):
pubmed: 32012900
Nature. 2019 Feb;566(7745):496-502
pubmed: 30787437
Front Cell Dev Biol. 2020 Sep 01;8:841
pubmed: 32984333
Mol Cells. 2014 Jul;37(7):562-7
pubmed: 25081036
J Cell Physiol. 2012 May;227(5):2264-75
pubmed: 21809343
Eur J Oral Sci. 2012 Dec;120(6):475-83
pubmed: 23167463
Lab Invest. 2016 Oct;96(10):1063-75
pubmed: 27479086
Dev Cell. 2012 Aug 14;23(2):317-28
pubmed: 22819339
Development. 2016 Nov 15;143(22):4115-4126
pubmed: 27660324
J Dent Res. 2013 Oct;92(10):899-904
pubmed: 23958762
Int J Mol Sci. 2020 Jun 19;21(12):
pubmed: 32575634
Arch Oral Biol. 2005 Aug;50(8):689-94
pubmed: 15958200
J Clin Periodontol. 2004 Mar;31(3):184-92
pubmed: 15016022
Biochem Biophys Res Commun. 2019 Feb 19;509(4):1008-1014
pubmed: 30654938
Stem Cell Res Ther. 2019 Jan 3;10(1):3
pubmed: 30606270
Front Physiol. 2020 Mar 05;11:174
pubmed: 32194440
Methods Mol Biol. 2021;2206:223-232
pubmed: 32754821
Genome Res. 2003 Sep;13(9):2129-41
pubmed: 12952881
Am J Pathol. 2000 Jul;157(1):287-95
pubmed: 10880398
J Cell Physiol. 2008 Dec;217(3):728-38
pubmed: 18663726
BMC Biol. 2019 Dec 13;17(1):104
pubmed: 31830989
Nature. 2016 Nov 24;539(7630):560-564
pubmed: 27851739
J Periodontol. 2012 May;83(5):672-9
pubmed: 21942790