Transcriptomic analysis reveals differential gene expression, alternative splicing, and novel exons during mouse trophoblast stem cell differentiation.
Alternative splicing
Differential expression
Placental development
RNA-seq
Stem cell differentiation
Trophoblast giant cells
Trophoblast stem cells
Journal
Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581
Informations de publication
Date de publication:
06 08 2020
06 08 2020
Historique:
received:
09
03
2020
accepted:
22
07
2020
revised:
15
07
2020
entrez:
9
8
2020
pubmed:
9
8
2020
medline:
25
5
2021
Statut:
epublish
Résumé
Differentiation of mouse trophoblast stem cells (TSCs) to trophoblast giant cells (TGCs) has been widely used as a model system to study placental development and function. While several differentially expressed genes, including regulators of TSC differentiation, have been identified, a comprehensive analysis of the global expression of genes and splice variants in the two cell types has not been reported. Here, we report ~ 7800 differentially expressed genes in TGCs compared to TSCs which include regulators of the cell cycle, apoptosis, cytoskeleton, cell mobility, embryo implantation, metabolism, and various signaling pathways. We show that several mitotic proteins, including Aurora A kinase, were downregulated in TGCs and that the activity of Aurora A kinase is required for the maintenance of TSCs. We also identify hitherto undiscovered, cell-type specific alternative splicing events in 31 genes in the two cell types. Finally, we also report 19 novel exons in 12 genes which are expressed in both TSCs and TGCs. Overall, our results uncover several potential regulators of TSC differentiation and TGC function, thereby providing a valuable resource for developmental and molecular biologists interested in the study of stem cell differentiation and embryonic development.
Sections du résumé
BACKGROUND
Differentiation of mouse trophoblast stem cells (TSCs) to trophoblast giant cells (TGCs) has been widely used as a model system to study placental development and function. While several differentially expressed genes, including regulators of TSC differentiation, have been identified, a comprehensive analysis of the global expression of genes and splice variants in the two cell types has not been reported.
RESULTS
Here, we report ~ 7800 differentially expressed genes in TGCs compared to TSCs which include regulators of the cell cycle, apoptosis, cytoskeleton, cell mobility, embryo implantation, metabolism, and various signaling pathways. We show that several mitotic proteins, including Aurora A kinase, were downregulated in TGCs and that the activity of Aurora A kinase is required for the maintenance of TSCs. We also identify hitherto undiscovered, cell-type specific alternative splicing events in 31 genes in the two cell types. Finally, we also report 19 novel exons in 12 genes which are expressed in both TSCs and TGCs.
CONCLUSIONS
Overall, our results uncover several potential regulators of TSC differentiation and TGC function, thereby providing a valuable resource for developmental and molecular biologists interested in the study of stem cell differentiation and embryonic development.
Identifiants
pubmed: 32762732
doi: 10.1186/s13287-020-01848-8
pii: 10.1186/s13287-020-01848-8
pmc: PMC7409654
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
342Références
Fetal Diagn Ther. 2001 Nov-Dec;16(6):364-71
pubmed: 11694740
J Cell Biol. 1998 Nov 2;143(3):695-707
pubmed: 9813091
Gene. 2016 May 10;582(1):1-13
pubmed: 26774798
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W465-7
pubmed: 15980513
Mol Cell Biol. 2007 Apr;27(7):2548-61
pubmed: 17210638
Development. 2005 May;132(9):2093-102
pubmed: 15788452
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Nature. 1997 Aug 21;388(6644):778-82
pubmed: 9285590
Oncotarget. 2017 Jun 20;8(25):41749-41763
pubmed: 28445157
Hum Reprod. 2008 Dec;23(12):2766-74
pubmed: 18718898
Cell Div. 2010 Jan 17;5:2
pubmed: 20180967
Am J Pathol. 2014 Dec;184(12):3321-31
pubmed: 25307528
Cell Stem Cell. 2012 Aug 3;11(2):179-94
pubmed: 22862944
Gene. 2013 Feb 1;514(1):1-30
pubmed: 22909801
Placenta. 2017 May;53:8-15
pubmed: 28487025
J Biol Chem. 2015 Sep 4;290(36):22019-29
pubmed: 26221038
Mech Dev. 2010 Jan-Feb;127(1-2):1-20
pubmed: 19755154
Oncogene. 2016 Jun 16;35(24):3083-91
pubmed: 26500059
Oncol Rep. 2019 Jan;41(1):154-164
pubmed: 30320346
Biol Reprod. 2017 Apr 1;96(4):733-742
pubmed: 28339967
Curr Stem Cell Res Ther. 2012 Nov;7(6):400-6
pubmed: 22953724
Placenta. 2005 Apr;26 Suppl A:S3-9
pubmed: 15837063
Reproduction. 2006 Apr;131(4):721-32
pubmed: 16595723
IUBMB Life. 2014 Feb;66(2):100-9
pubmed: 24574067
Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16189-94
pubmed: 18838676
Placenta. 2015 Dec;36(12):1342-51
pubmed: 26515927
Nature. 2000 Mar 2;404(6773):95-9
pubmed: 10716450
Dev Biol. 2007 Feb 1;302(1):143-53
pubmed: 17027741
Histol Histopathol. 2013 Jul;28(7):817-25
pubmed: 23450430
Genome Biol. 2014;15(12):550
pubmed: 25516281
Cell Cycle. 2009 May 15;8(10):1501-9
pubmed: 19372757
Int J Dev Biol. 2010;54(2-3):341-54
pubmed: 19876834
Oncotarget. 2015 May 10;6(13):11162-74
pubmed: 25883213
J Reprod Immunol. 2013 Mar;97(1):43-50
pubmed: 23432871
Sci Rep. 2017 Feb 23;7:42941
pubmed: 28230167
Nucleic Acids Res. 2016 Sep 6;44(15):e127
pubmed: 27257077
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Genes Dev. 2008 Nov 1;22(21):3024-36
pubmed: 18981479
Placenta. 2009 Mar;30 Suppl A:S49-54
pubmed: 19027159
Cell. 2009 Feb 6;136(3):566, 566.e1
pubmed: 19203588
Biochim Biophys Acta. 2003 Apr 7;1640(1):25-31
pubmed: 12676351
Sci Rep. 2018 Apr 11;8(1):5811
pubmed: 29643413
J Cell Sci. 2015 Apr 1;128(7):1294-307
pubmed: 25673876
Dev Biol. 2001 Feb 1;230(1):43-60
pubmed: 11161561
Semin Reprod Med. 2009 Jan;27(1):62-79
pubmed: 19197806
Mol Cell Biol. 2010 Jul;30(13):3310-20
pubmed: 20404091
Clin Chim Acta. 2019 Aug;495:637-645
pubmed: 29329728
Nat Rev Mol Cell Biol. 2012 Dec;13(12):789-803
pubmed: 23175282
Stem Cell Res. 2018 Aug;31:135-146
pubmed: 30086473
Development. 2008 Oct;135(19):3311-20
pubmed: 18776147
Nat Genet. 2005 May;37(5):514-9
pubmed: 15806103
PLoS One. 2014 May 21;9(5):e97434
pubmed: 24848107
Placenta. 1993 Mar-Apr;14(2):187-201
pubmed: 8506250
Science. 1998 Dec 11;282(5396):2072-5
pubmed: 9851926
Dev Biol. 2001 Jul 15;235(2):422-32
pubmed: 11437448
Development. 2009 Apr;136(8):1363-74
pubmed: 19304888
Am J Obstet Gynecol. 2015 Oct;213(4 Suppl):S115-22
pubmed: 26428489
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Biol Reprod. 2018 Nov 1;99(5):982-999
pubmed: 29901777
BMC Bioinformatics. 2012 Jun 18;13:134
pubmed: 22708584
Reprod Biol Endocrinol. 2004 Jul 05;2:47
pubmed: 15236655
Nucleic Acids Res. 2016 Jan 4;44(D1):D840-7
pubmed: 26578600
Dev Biol. 2007 Apr 15;304(2):567-78
pubmed: 17289015
Reproduction. 2016 Oct 14;:
pubmed: 27742864
Cell Div. 2009 Jun 02;4:10
pubmed: 19490616
Trends Endocrinol Metab. 2007 Apr;18(3):114-21
pubmed: 17324580
BMC Dev Biol. 2010 Sep 14;10:97
pubmed: 20840781
Mol Cell Biol. 2011 Oct;31(19):4129-43
pubmed: 21791608
Sci Rep. 2017 Aug 15;7(1):8163
pubmed: 28811571
Biol Reprod. 2011 Mar;84(3):412-21
pubmed: 21106963
Placenta. 2018 Jun;66:57-64
pubmed: 29884303
Biol Reprod. 2016 Nov;95(5):110
pubmed: 27683262
Placenta. 2004 Apr;25 Suppl A:S32-8
pubmed: 15033304
APMIS. 2018 Jul;126(7):613-620
pubmed: 30129132
J Biol Chem. 2010 Jul 9;285(28):21849-57
pubmed: 20444701
Sci Rep. 2018 Feb 19;8(1):3305
pubmed: 29459693
J Clin Invest. 2004 Sep;114(6):744-54
pubmed: 15372095
J Cell Biol. 2003 May 26;161(4):749-56
pubmed: 12771125
Stem Cells. 2019 Oct;37(10):1307-1318
pubmed: 31233251
Cell Stem Cell. 2013 Jan 3;12(1):15-30
pubmed: 23290134
J Biol Chem. 2015 Dec 11;290(50):30152-62
pubmed: 26491013
EMBO J. 2000 Oct 2;19(19):5060-70
pubmed: 11013209
Nucleic Acids Res. 2019 Jan 8;47(D1):D330-D338
pubmed: 30395331
Oncotarget. 2017 Jan 31;8(5):8283-8293
pubmed: 28030818
Dev Biol. 2014 Mar 1;387(1):49-63
pubmed: 24412371
Biochemistry. 2006 Nov 21;45(46):13818-26
pubmed: 17105200
Genome Res. 2003 Sep;13(9):2129-41
pubmed: 12952881
Cell Adh Migr. 2016 Mar 3;10(1-2):88-110
pubmed: 26743330
Stem Cell Res. 2014 Nov;13(3 Pt A):478-91
pubmed: 25239494
Genes Dev. 2001 Apr 1;15(7):833-8
pubmed: 11297507