High-throughput micropatterning platform reveals Nodal-dependent bisection of peri-gastrulation-associated versus preneurulation-associated fate patterning.
Biomechanical Phenomena
Body Patterning
/ genetics
Bone Morphogenetic Protein 4
/ genetics
Cell Culture Techniques
Cell Differentiation
/ drug effects
Cell Line
Cell Lineage
/ drug effects
Gastrulation
/ drug effects
Gene Expression Profiling
Gene Expression Regulation, Developmental
Genetic Heterogeneity
High-Throughput Screening Assays
Humans
Models, Biological
Neurogenesis
/ drug effects
Nodal Protein
/ genetics
Pluripotent Stem Cells
/ cytology
Signal Transduction
Surface Properties
Journal
PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
17
10
2018
accepted:
25
09
2019
revised:
31
10
2019
pubmed:
22
10
2019
medline:
26
2
2020
entrez:
22
10
2019
Statut:
epublish
Résumé
In vitro models of postimplantation human development are valuable to the fields of regenerative medicine and developmental biology. Here, we report characterization of a robust in vitro platform that enabled high-content screening of multiple human pluripotent stem cell (hPSC) lines for their ability to undergo peri-gastrulation-like fate patterning upon bone morphogenetic protein 4 (BMP4) treatment of geometrically confined colonies and observed significant heterogeneity in their differentiation propensities along a gastrulation associable and neuralization associable axis. This cell line-associated heterogeneity was found to be attributable to endogenous Nodal expression, with up-regulation of Nodal correlated with expression of a gastrulation-associated gene profile, and Nodal down-regulation correlated with a preneurulation-associated gene profile expression. We harness this knowledge to establish a platform of preneurulation-like fate patterning in geometrically confined hPSC colonies in which fates arise because of a BMPs signalling gradient conveying positional information. Our work identifies a Nodal signalling-dependent switch in peri-gastrulation versus preneurulation-associated fate patterning in hPSC cells, provides a technology to robustly assay hPSC differentiation outcomes, and suggests conserved mechanisms of organized fate specification in differentiating epiblast and ectodermal tissues.
Identifiants
pubmed: 31634368
doi: 10.1371/journal.pbio.3000081
pii: PBIOLOGY-D-18-00978
pmc: PMC6822778
doi:
Substances chimiques
BMP4 protein, human
0
Bone Morphogenetic Protein 4
0
NODAL protein, human
0
Nodal Protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3000081Subventions
Organisme : CIHR
ID : 375257
Pays : Canada
Organisme : Wellcome Trust
ID : 206439/Z/17/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P018823/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_12026
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Lab Chip. 2009 Jun 7;9(11):1640-2
pubmed: 19458875
PLoS One. 2008 Jan 02;3(1):e1384
pubmed: 18167543
Philos Trans R Soc Lond B Biol Sci. 1981 Oct 7;295(1078):441-50
pubmed: 6117904
Kybernetik. 1972 Dec;12(1):30-9
pubmed: 4663624
Dev Cell. 2005 Oct;9(4):523-33
pubmed: 16198294
Development. 2012 Mar;139(6):1175-87
pubmed: 22318231
Curr Opin Genet Dev. 2006 Aug;16(4):419-25
pubmed: 16793258
Kidney Int. 2010 Mar;77(5):407-16
pubmed: 20016472
Nat Methods. 2014 Aug;11(8):847-54
pubmed: 24973948
Nucleic Acids Res. 2014 Dec 16;42(22):e168
pubmed: 25300484
Nat Rev Mol Cell Biol. 2013 Aug;14(8):467-73
pubmed: 23839578
Cell Stem Cell. 2007 Sep 13;1(3):253-8
pubmed: 18371359
Nat Methods. 2011 Apr;8(4):315-7
pubmed: 21378979
Nature. 2012 Jan 18;481(7381):295-305
pubmed: 22258608
Curr Opin Genet Dev. 2017 Oct;46:179-185
pubmed: 28843810
Methods Mol Biol. 2010;649:247-56
pubmed: 20680839
Dev Biol. 2005 Feb 1;278(1):255-63
pubmed: 15649477
Anal Chem. 2011 May 1;83(9):3379-85
pubmed: 21413805
Development. 2002 Aug;129(15):3597-608
pubmed: 12117810
Development. 2017 Apr 1;144(7):1146-1158
pubmed: 28351865
Nat Biotechnol. 2016 Feb;34(2):184-191
pubmed: 26780180
Development. 2015 Dec 1;142(23):3996-4009
pubmed: 26628090
Nat Rev Genet. 2018 Oct;19(10):595-614
pubmed: 30089805
J Theor Biol. 1969 Oct;25(1):1-47
pubmed: 4390734
Nature. 1988 Dec 22-29;336(6201):772-4
pubmed: 3205305
Development. 2017 Dec 1;144(23):4298-4312
pubmed: 28870989
Dev Cell. 2016 Nov 7;39(3):302-315
pubmed: 27746044
Nat Mater. 2018 Jul;17(7):571-572
pubmed: 29941948
Stem Cell Reports. 2016 Sep 13;7(3):496-507
pubmed: 27594587
PLoS Biol. 2017 Oct 19;15(10):e2004045
pubmed: 29049289
Am J Anat. 1956 May;98(3):435-93
pubmed: 13362122
Annu Rev Neurosci. 2014;37:221-42
pubmed: 25032496
Annu Rev Biomed Eng. 2001;3:335-73
pubmed: 11447067
Development. 2017 Feb 15;144(4):552-566
pubmed: 28196803
Cell Stem Cell. 2015 Jun 4;16(6):639-52
pubmed: 25921273
Elife. 2014 May 21;3:e01817
pubmed: 24850665
Nature. 2013 Sep 19;501(7467):373-9
pubmed: 23995685
Dev Cell. 2004 Aug;7(2):155-64
pubmed: 15296713
PLoS Comput Biol. 2019 Jan 2;15(1):e1006384
pubmed: 30601802
Nat Cell Biol. 2016 Jun;18(6):700-708
pubmed: 27144686
Curr Top Dev Biol. 2018;129:1-23
pubmed: 29801527
Elife. 2016 Apr 08;5:
pubmed: 27058171
Science. 2006 Dec 1;314(5804):1447-50
pubmed: 17082421
Hum Reprod Update. 2018 Jan 25;:null
pubmed: 29377992
Genes Dev. 2011 Feb 1;25(3):238-50
pubmed: 21245162
Prenat Diagn. 2009 Apr;29(4):303-11
pubmed: 19206138
Cell. 2017 Mar 23;169(1):161-173.e12
pubmed: 28340341
Vitam Horm. 2015;99:63-90
pubmed: 26279373
Development. 2008 Aug;135(15):2489-503
pubmed: 18621990
Cell Stem Cell. 2014 Jan 2;14(1):107-20
pubmed: 24139757
Stem Cells. 2008 Sep;26(9):2300-10
pubmed: 18583540
Science. 2012 May 11;336(6082):721-4
pubmed: 22499809
Dev Cell. 2016 Sep 26;38(6):590-600
pubmed: 27676432
Nat Methods. 2013 Dec;10(12):1225-31
pubmed: 24141495
Methods Cell Biol. 2010;97:133-46
pubmed: 20719269
Nat Biotechnol. 2015 Nov;33(11):1182-92
pubmed: 26501952
Nature. 2016 May 04;533(7602):251-4
pubmed: 27144363
Sci Rep. 2016 Feb 09;6:20664
pubmed: 26857385
Dev Biol. 2014 May 1;389(1):2-12
pubmed: 24321819
Genome Res. 2013 Jul;23(7):1069-80
pubmed: 23817048
Nat Rev Genet. 2007 May;8(5):368-81
pubmed: 17387317
Development. 2015 Jan 15;142(2):242-57
pubmed: 25564621
Anal Chem. 2004 Jul 1;76(13):3675-81
pubmed: 15228340
Stem Cell Reports. 2015 Apr 14;4(4):591-604
pubmed: 25843049
Biomaterials. 1999 Dec;20(23-24):2363-76
pubmed: 10614942
Nat Commun. 2012;3:1070
pubmed: 22990866
Methods Mol Biol. 2009;482:21-33
pubmed: 19089347
J Cell Sci. 2010 Dec 15;123(Pt 24):4201-13
pubmed: 21123618
Nat Mater. 2018 Jul;17(7):633-641
pubmed: 29784997
Angew Chem Int Ed Engl. 2010 Aug 23;49(36):6288-308
pubmed: 20648499
Nature. 2007 Nov 29;450(7170):717-20
pubmed: 18046410
Elife. 2017 Dec 07;6:
pubmed: 29215332
Development. 2015 Apr 1;142(7):1203-11
pubmed: 25804733