Spatiotemporal analysis of human intestinal development at single-cell resolution.
Endothelial Cells
/ cytology
Enteric Nervous System
/ cytology
Fetus
/ embryology
Fibroblasts
/ cytology
Humans
Immunity
Intestinal Diseases
/ congenital
Intestinal Mucosa
/ growth & development
Intestines
/ blood supply
Ligands
Mesoderm
/ cytology
Neovascularization, Physiologic
Pericytes
/ cytology
Single-Cell Analysis
Stem Cells
/ cytology
Time Factors
Transcription Factors
/ metabolism
congenital disease
gene expression
human development
human developmental cell atlas
intestinal crypt
intestinal development
mesenchymal cells
single-cell RNA-sequencing
spatial transcriptomics
stem cells
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
04 02 2021
04 02 2021
Historique:
received:
10
08
2020
revised:
10
10
2020
accepted:
10
12
2020
pubmed:
7
1
2021
medline:
25
8
2021
entrez:
6
1
2021
Statut:
ppublish
Résumé
Development of the human intestine is not well understood. Here, we link single-cell RNA sequencing and spatial transcriptomics to characterize intestinal morphogenesis through time. We identify 101 cell states including epithelial and mesenchymal progenitor populations and programs linked to key morphogenetic milestones. We describe principles of crypt-villus axis formation; neural, vascular, mesenchymal morphogenesis, and immune population of the developing gut. We identify the differentiation hierarchies of developing fibroblast and myofibroblast subtypes and describe diverse functions for these including as vascular niche cells. We pinpoint the origins of Peyer's patches and gut-associated lymphoid tissue (GALT) and describe location-specific immune programs. We use our resource to present an unbiased analysis of morphogen gradients that direct sequential waves of cellular differentiation and define cells and locations linked to rare developmental intestinal disorders. We compile a publicly available online resource, spatio-temporal analysis resource of fetal intestinal development (STAR-FINDer), to facilitate further work.
Identifiants
pubmed: 33406409
pii: S0092-8674(20)31686-X
doi: 10.1016/j.cell.2020.12.016
pmc: PMC7864098
pii:
doi:
Substances chimiques
Ligands
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
810-826.e23Subventions
Organisme : Medical Research Council
ID : MR/M00919X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00008/7
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12010/7
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R006237/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S036377/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 219523/Z/19/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S036334/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 216419/Z/19/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_MR/S025952/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
Dev Dyn. 2007 Jul;236(7):2020-5
pubmed: 17576138
Dev Cell. 2009 Apr;16(4):588-99
pubmed: 19386267
Nature. 2019 Oct;574(7778):365-371
pubmed: 31597962
Cell. 2019 Dec 12;179(7):1647-1660.e19
pubmed: 31835037
Nat Biotechnol. 2011 Nov 13;29(12):1120-7
pubmed: 22081019
Development. 2006 Mar;133(5):833-43
pubmed: 16439479
Science. 2016 Jul 1;353(6294):78-82
pubmed: 27365449
Nature. 2018 Aug;560(7719):494-498
pubmed: 30089906
Cell. 2020 Feb 20;180(4):764-779.e20
pubmed: 32059779
Physiology (Bethesda). 2016 Sep;31(5):316-26
pubmed: 27488743
BMC Biol. 2017 May 19;15(1):45
pubmed: 28526034
Cell. 2014 Apr 24;157(3):714-25
pubmed: 24766814
Hum Mol Genet. 2019 Mar 1;28(5):828-841
pubmed: 30445423
Nature. 2018 Jun;558(7710):449-453
pubmed: 29875413
Brief Bioinform. 2013 Mar;14(2):144-61
pubmed: 22908213
Dev Dyn. 2009 Jan;238(1):29-42
pubmed: 19097184
Cell Stem Cell. 2020 Mar 5;26(3):391-402.e5
pubmed: 32084389
Development. 2005 Dec;132(23):5317-28
pubmed: 16284122
Cell. 2020 Sep 17;182(6):1606-1622.e23
pubmed: 32888429
Am J Physiol Gastrointest Liver Physiol. 2006 Jun;290(6):G1194-202
pubmed: 16195423
Trends Mol Med. 2015 Aug;21(8):492-503
pubmed: 26144290
J Biol Chem. 1997 Mar 7;272(10):6812-7
pubmed: 9045716
Am J Physiol Gastrointest Liver Physiol. 2011 May;300(5):G684-96
pubmed: 21252048
Development. 2011 Nov;138(21):4789-800
pubmed: 21989918
Anat Embryol (Berl). 2004 Apr;208(1):33-41
pubmed: 14991401
Exp Cell Res. 2017 Oct 15;359(2):449-457
pubmed: 28830685
J Clin Invest. 2012 Dec;122(12):4680-4
pubmed: 23114594
Nat Rev Mol Cell Biol. 2021 Jan;22(1):39-53
pubmed: 32958874
Cell. 2018 Aug 23;174(5):1293-1308.e36
pubmed: 29961579
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Nat Cell Biol. 2012 Oct;14(10):1099-1104
pubmed: 23000963
Nat Commun. 2018 Jul 10;9(1):2667
pubmed: 29991676
Sci Rep. 2019 Dec 20;9(1):19489
pubmed: 31862906
Nature. 2007 Mar 29;446(7135):547-51
pubmed: 17322904
Genome Biol. 2014;15(12):550
pubmed: 25516281
J Biol Chem. 2004 Apr 9;279(15):14792-802
pubmed: 14739280
J Morphol. 1972 Jun;137(2):193-213
pubmed: 4555575
Int J Clin Exp Pathol. 2018 Mar 01;11(3):1629-1636
pubmed: 31938262
Differentiation. 2016 Sep;92(3):116-131
pubmed: 27165847
Science. 2017 May 19;356(6339):722-726
pubmed: 28522527
Cell. 2018 Nov 1;175(4):1156-1167.e15
pubmed: 30270040
J Exp Med. 2020 Feb 3;217(2):
pubmed: 31753849
Science. 2017 Apr 21;356(6335):
pubmed: 28428369
Cell Death Differ. 2013 Mar;20(3):369-81
pubmed: 23154389
J Immunol. 2001 Sep 1;167(5):2511-21
pubmed: 11509590
Nat Methods. 2017 Oct;14(10):979-982
pubmed: 28825705
Genome Biol. 2019 Dec 23;20(1):296
pubmed: 31870423
Nat Methods. 2019 Dec;16(12):1289-1296
pubmed: 31740819
Am J Hum Genet. 2018 Jan 4;102(1):27-43
pubmed: 29276006
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D493-6
pubmed: 14681465
Physiol Genomics. 2010 Jun;42(1):115-25
pubmed: 20354101
Eur J Neurosci. 2016 Jun;43(11):1449-59
pubmed: 26913565
Blood. 2019 Sep 26;134(13):1059-1071
pubmed: 31383639
Nat Cell Biol. 2018 Jun;20(6):721-734
pubmed: 29802404
Cell. 2018 Oct 4;175(2):372-386.e17
pubmed: 30270042
Genome Biol. 2019 Mar 22;20(1):63
pubmed: 30902100
Nat Methods. 2017 Nov;14(11):1083-1086
pubmed: 28991892
Cell. 2020 Jun 11;181(6):1291-1306.e19
pubmed: 32407674
Nat Commun. 2019 Jan 21;10(1):365
pubmed: 30664649
Cell. 2015 Apr 23;161(3):569-580
pubmed: 25865482
BMC Pediatr. 2018 Nov 27;18(1):372
pubmed: 30482190
Mol Cell Biol. 2003 Dec;23(24):9104-16
pubmed: 14645522
Cell. 2021 Feb 4;184(3):810-826.e23
pubmed: 33406409
Genes Dev. 1997 Jun 15;11(12):1583-95
pubmed: 9203584
Exp Hematol. 2018 Dec;68:51-61
pubmed: 30243574
Nature. 2019 Mar;567(7746):49-55
pubmed: 30814735
Br J Haematol. 1991 Feb;77(2):229-36
pubmed: 2004025
Development. 2010 Jul;137(13):2187-96
pubmed: 20530546
PLoS One. 2017 Apr 20;12(4):e0176031
pubmed: 28426719
Science. 2013 Oct 11;342(6155):212-8
pubmed: 23989955
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
J Neurosci. 2013 May 22;33(21):9122-39
pubmed: 23699523
Dev Cell. 2020 Dec 21;55(6):771-783.e5
pubmed: 33290721
J Biol Chem. 2008 Mar 14;283(11):6832-42
pubmed: 18192275
Nat Rev Gastroenterol Hepatol. 2018 Mar;15(3):152-167
pubmed: 29300049
Cell. 2018 Aug 23;174(5):1277-1292.e14
pubmed: 30142345
Nucleic Acids Res. 2019 Jan 8;47(D1):D1018-D1027
pubmed: 30476213
Gastroenterology. 2009 Jun;136(7):2074-91
pubmed: 19303014
Gastroenterology. 2009 Dec;137(6):2052-62
pubmed: 19737569
J Exp Med. 2007 May 14;204(5):1119-30
pubmed: 17452521
Nat Commun. 2018 Jan 18;9(1):284
pubmed: 29348443
Immunity. 2019 Feb 19;50(2):462-476.e8
pubmed: 30770246
Nucleic Acids Res. 2019 Jan 8;47(D1):D607-D613
pubmed: 30476243
Nature. 2018 May;557(7704):242-246
pubmed: 29720649
Cell Tissue Res. 2015 Aug;361(2):557-65
pubmed: 25795141
Development. 2007 Jul;134(13):2521-31
pubmed: 17522155
Dev Dyn. 2016 May;245(5):614-26
pubmed: 26930384
Cell. 2020 Apr 16;181(2):442-459.e29
pubmed: 32302573
Front Immunol. 2018 Nov 27;9:2733
pubmed: 30538701
Cell Mol Gastroenterol Hepatol. 2016 Mar;2(2):189-209
pubmed: 27066525
Nutrients. 2018 Jun 05;10(6):
pubmed: 29874829
Cell. 2019 Feb 21;176(5):1158-1173.e16
pubmed: 30712869
J Pediatr Surg. 2009 Jun;44(6):1072-5; discussion 1075-6
pubmed: 19524719
Cell. 2019 Jul 25;178(3):714-730.e22
pubmed: 31348891
BMC Bioinformatics. 2008 Dec 29;9:559
pubmed: 19114008
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Genome Biol. 2018 Dec 19;19(1):224
pubmed: 30567574
Eur J Hum Genet. 2009 Sep;17(9):1141-7
pubmed: 19277063
Genome Biol. 2019 Mar 19;20(1):59
pubmed: 30890159
Immunology. 2019 Dec;158(4):267-280
pubmed: 31509239
Cell Res. 2016 Oct;26(10):1079-1098
pubmed: 27364685
Cell Stem Cell. 2020 Nov 25;:
pubmed: 33278341
J Embryol Exp Morphol. 1958 Sep;6(3):403-11
pubmed: 13575653
J Exp Med. 2003 May 5;197(9):1199-204
pubmed: 12732661
Cell. 2019 Sep 5;178(6):1493-1508.e20
pubmed: 31474370
J Biol Chem. 2015 Mar 20;290(12):7563-75
pubmed: 25631042
Dev Dyn. 2011 Mar;240(3):501-20
pubmed: 21246663
Cell Tissue Res. 2005 Mar;319(3):367-82
pubmed: 15672264
Development. 2016 Feb 1;143(3):427-36
pubmed: 26721501
Nature. 2017 Nov 16;551(7680):333-339
pubmed: 29144463
Cell Mol Life Sci. 2003 Jul;60(7):1322-32
pubmed: 12943221
Early Hum Dev. 2014 Dec;90(12):921-5
pubmed: 25448782
Genome Biol. 2015 Dec 10;16:278
pubmed: 26653891
Nat Cell Biol. 2012 Dec;14(12):1251-60
pubmed: 23143399
JCI Insight. 2017 Mar 23;2(6):e91738
pubmed: 28352663
Genome Biol. 2008 Jan 24;9(1):R17
pubmed: 18218067
Dev Biol. 2008 Nov 15;323(2):177-88
pubmed: 18804460
Mol Cell Biol. 2003 Apr;23(7):2425-37
pubmed: 12640126
Am J Physiol Gastrointest Liver Physiol. 2001 May;280(5):G1022-9
pubmed: 11292612
Nat Rev Gastroenterol Hepatol. 2012 Nov;9(11):625-32
pubmed: 22890111
Nat Rev Immunol. 2010 Sep;10(9):664-74
pubmed: 20706277
Nat Rev Mol Cell Biol. 2014 Jan;15(1):19-33
pubmed: 24326621
Biochem Biophys Res Commun. 2019 Dec 3;520(2):304-310
pubmed: 31601422
Nucleic Acids Res. 2020 Jun 4;48(10):e55
pubmed: 32196115