Rapid retinoic acid-induced trophoblast cell model from human induced pluripotent stem cells.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
06 Aug 2024
06 Aug 2024
Historique:
received:
31
01
2024
accepted:
30
07
2024
medline:
7
8
2024
pubmed:
7
8
2024
entrez:
6
8
2024
Statut:
epublish
Résumé
A limited number of accessible and representative models of human trophoblast cells currently exist for the study of placentation. Current stem cell models involve either a transition through a naïve stem cell state or precise dynamic control of multiple growth factors and small-molecule cues. Here, we demonstrated that a simple five-day treatment of human induced pluripotent stem cells with two small molecules, retinoic acid (RA) and Wnt agonist CHIR 99021 (CHIR), resulted in rapid, synergistic upregulation of CDX2. Transcriptomic analysis of RA + CHIR-treated cells showed high similarity to primary trophectoderm cells. Multipotency was verified via further differentiation towards cells with syncytiotrophoblast or extravillous trophoblast features. RA + CHIR-treated cells were also assessed for the established criteria defining a trophoblast cell model, and they possess all the features necessary to be considered valid. Collectively, our data demonstrate a facile, scalable method for generating functional trophoblast-like cells in vitro to better understand the placenta.
Identifiants
pubmed: 39107470
doi: 10.1038/s41598-024-68952-0
pii: 10.1038/s41598-024-68952-0
doi:
Substances chimiques
Tretinoin
5688UTC01R
Pyridines
0
Chir 99021
0
CDX2 Transcription Factor
0
Pyrimidines
0
CDX2 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
18204Subventions
Organisme : NIH HHS
ID : NIH DK 114453
Pays : United States
Organisme : NIH HHS
ID : NIH DK 114453
Pays : United States
Organisme : NIH HHS
ID : NIH DK 114453
Pays : United States
Organisme : National Science Foundation
ID : Graduate Research Fellowship
Informations de copyright
© 2024. The Author(s).
Références
Latos, P. A. & Hemberger, M. From the stem of the placental tree: Trophoblast stem cells and their progeny. Dev. Camb. 143, 3650–3660 (2016).
Knöfler, M. et al. Human placenta and trophoblast development: Key molecular mechanisms and model systems. Cell. Mol. Life Sci. 76, 3479–3496 (2019).
pubmed: 31049600
pmcid: 6697717
doi: 10.1007/s00018-019-03104-6
Okae, H. et al. Derivation of human trophoblast stem cells. Cell Stem Cell 22, 50-63.e6 (2018).
pubmed: 29249463
doi: 10.1016/j.stem.2017.11.004
Bilban, M. et al. Trophoblast invasion: Assessment of cellular models using gene expression signatures. Placenta 31, 989–996 (2010).
pubmed: 20850871
doi: 10.1016/j.placenta.2010.08.011
Tan, J. P., Liu, X. & Polo, J. M. Establishment of human induced trophoblast stem cells via reprogramming of fibroblasts. Nat. Protoc. 17, 2739–2759 (2022).
pubmed: 36241724
doi: 10.1038/s41596-022-00742-2
Castel, G. & David, L. Induction of human trophoblast stem cells. Nat. Protoc. 17, 2760–2783 (2022).
pubmed: 36241723
doi: 10.1038/s41596-022-00744-0
Blakeley, P. et al. Defining the three cell lineages of the human blastocyst by single-cell RNA-seq. Development 142, 3613 (2015).
pubmed: 26487783
pmcid: 4631772
doi: 10.1242/dev.131235
Molè, M. A., Weberling, A. & Zernicka-Goetz, M. Comparative analysis of human and mouse development: From zygote to pre-gastrulation. Current Topics in Developmental Biology vol. 136 (Elsevier Inc., 2020).
Fogarty, N. M. E. et al. Genome editing reveals a role for OCT4 in human embryogenesis. Nature 550, 67–73 (2017).
pubmed: 28953884
pmcid: 5815497
doi: 10.1038/nature24033
Kuckenberg, P. et al. The transcription factor TCFAP2C/AP-2γ Cooperates with CDX2 to maintain trophectoderm formation. Mol. Cell. Biol. 30, 3310–3320 (2010).
pubmed: 20404091
pmcid: 2897582
doi: 10.1128/MCB.01215-09
Ralston, A. et al. Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2. Development 137, 395–403 (2010).
pubmed: 20081188
doi: 10.1242/dev.038828
Xu, R. H. et al. BMP4 initiates human embryonic stem cell differentiation to trophoblast. Nat. Biotechnol. 20, 1261–1264 (2002).
pubmed: 12426580
doi: 10.1038/nbt761
Horii, M., Bui, T., Touma, O., Cho, H. Y. & Parast, M. M. An improved two-step protocol for trophoblast differentiation of human pluripotent stem cells. Curr. Protoc. Stem Cell Biol. 50 (2019).
Cambuli, F. et al. Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast. Nat. Commun. 5, 1–16 (2014).
doi: 10.1038/ncomms6538
Roberts, R. M. et al. Differentiation of trophoblast cells from human embryonic stem cells: To be or not to be? Reproduction 147 (2014).
Lee, C. Q. E. et al. What is trophoblast? A combination of criteria define human first-trimester trophoblast. Stem Cell Rep. 6, 257–272 (2016).
doi: 10.1016/j.stemcr.2016.01.006
Mischler, A. et al. Two distinct trophectoderm lineage stem cells from human pluripotent stem cells. J. Biol. Chem. 296 (2021).
Dong, C. et al. Derivation of trophoblast stem cells from naïve human pluripotent stem cells. eLife 9, 1–26 (2020).
doi: 10.7554/eLife.52504
Guo, G. et al. Human naive epiblast cells possess unrestricted lineage potential. Cell Stem Cell 28, 1040-1056.e6 (2021).
pubmed: 33831366
pmcid: 8189439
doi: 10.1016/j.stem.2021.02.025
Jagtap, S. et al. All-trans retinoic acid and basic fibroblast growth factor synergistically direct pluripotent human embryonic stem cells to extraembryonic lineages. Stem Cell Res. 10, 228–240 (2013).
pubmed: 23314291
doi: 10.1016/j.scr.2012.12.002
Knöfler, M. & Pollheimer, J. Human placental trophoblast invasion and differentiation: A particular focus on Wnt signaling. Front. Genet. 4, 190 (2013).
pubmed: 24133501
pmcid: 3783976
doi: 10.3389/fgene.2013.00190
Horii, M. et al. Human pluripotent stem cells as a model of trophoblast differentiation in both normal development and disease. Proc. Natl. Acad. Sci. USA 113, E3882–E3891 (2016).
pubmed: 27325764
pmcid: 4941448
doi: 10.1073/pnas.1604747113
Niakan, K. K. & Eggan, K. Analysis of human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse. Dev. Biol. 375, 54–64 (2013).
pubmed: 23261930
doi: 10.1016/j.ydbio.2012.12.008
Wang, C. C., Jamal, L. & Janes, K. A. Normal morphogenesis of epithelial tissues and progression of epithelial tumors. Wiley Interdiscip. Rev. Syst. Biol. Med. 4, 51–78 (2012).
pubmed: 21898857
doi: 10.1002/wsbm.159
Li, Z., Kurosawa, O. & Iwata, H. Establishment of human trophoblast stem cells from human induced pluripotent stem cell-derived cystic cells under micromesh culture. Stem Cell Res. Ther. 10 (2019).
Krendl, C. et al. GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency. Proc. Natl. Acad. Sci. USA 114, E9579–E9588 (2017).
pubmed: 29078328
pmcid: 5692555
doi: 10.1073/pnas.1708341114
Blanchon, L. et al. Activation of the human pregnancy-specific glycoprotein PSG-5 promoter by KLF4 and Sp1. Biochem. Biophys. Res. Commun. 343, 745–753 (2006).
pubmed: 16563348
doi: 10.1016/j.bbrc.2006.03.032
Donker, R. B. et al. The expression profile of C19MC microRNAs in primary human trophoblast cells and exosomes. Mol. Hum. Reprod. 18, 417–424 (2012).
pubmed: 22383544
pmcid: 3389496
doi: 10.1093/molehr/gas013
Soncin, F. et al. Derivation of functional trophoblast stem cells from primed human pluripotent stem cells. Stem Cell Rep. 17, 1303–1317 (2022).
doi: 10.1016/j.stemcr.2022.04.013
Zhou, F. et al. Reconstituting the transcriptome and DNA methylome landscapes of human implantation. Nature 572, 660–664 (2019).
pubmed: 31435013
doi: 10.1038/s41586-019-1500-0
Chang, C. W., Wakeland, A. K. & Parast, M. M. Trophoblast lineage specification, differentiation and their regulation by oxygen tension. J. Endocrinol. 236, R43–R56 (2018).
pubmed: 29259074
pmcid: 5741095
doi: 10.1530/JOE-17-0402
Hutchins, A. P. et al. Models of global gene expression define major domains of cell type and tissue identity. Nucleic Acids Res. 45, 2354–2367 (2017).
pubmed: 28426095
pmcid: 5389706
doi: 10.1093/nar/gkx054
Du, R. et al. Hypoxia-induced down-regulation of microRNA-34a promotes EMT by targeting the Notch signaling pathway in tubular epithelial cells. PLoS ONE 7, e30771 (2012).
pubmed: 22363487
pmcid: 3281867
doi: 10.1371/journal.pone.0030771
Haider, S. et al. Self-renewing trophoblast organoids recapitulate the developmental program of the early human placenta. Stem Cell Rep. 11, 537–551 (2018).
doi: 10.1016/j.stemcr.2018.07.004
Apps, R. et al. Human leucocyte antigen (HLA) expression of primary trophoblast cells and placental cell lines, determined using single antigen beads to characterize allotype specificities of anti-HLA antibodies. Immunology 127, 26–39 (2009).
pubmed: 19368562
pmcid: 2678179
doi: 10.1111/j.1365-2567.2008.03019.x
Davies, E. et al. Epithelial-mesenchymal transition during extravillous trophoblast differentiation. Cell Adhes. Migr. 10, 310–321 (2016).
doi: 10.1080/19336918.2016.1170258
Papuchova, H. & Latos, P. A. Transcription factor networks in trophoblast development. Cell. Mol. Life Sci. 79, 337 (2022).
pubmed: 35657505
pmcid: 9166831
doi: 10.1007/s00018-022-04363-6
Jeyarajah, M. J. et al. The multifaceted role of GCM1 during trophoblast differentiation in the human placenta. Proc. Natl. Acad. Sci. U. S. A. 119, (2022).
Green, B. B. et al. The role of placental 11-beta hydroxysteroid dehydrogenase type 1 and type 2 methylation on gene expression and infant birth weight. Biol. Reprod. 92, 149–150 (2015).
pubmed: 25788665
pmcid: 4652612
doi: 10.1095/biolreprod.115.128066
Hemberger, M., Udayashankar, R., Tesar, P., Moore, H. & Burton, G. J. ELF5-enforced transcriptional networks define an epigenetically regulated trophoblast stem cell compartment in the human placenta. Hum. Mol. Genet. 19, 2456–2467 (2010).
pubmed: 20354077
doi: 10.1093/hmg/ddq128
Kobayashi, N. et al. The microRNA cluster C19MC confers differentiation potential into trophoblast lineages upon human pluripotent stem cells. Nat. Commun. 13, 1–14 (2022).
doi: 10.1038/s41467-022-30775-w
Karvas, R. M. et al. Stem-cell-derived trophoblast organoids model human placental development and susceptibility to emerging pathogens. Cell Stem Cell 29, 810-825.e8 (2022).
pubmed: 35523141
pmcid: 9136997
doi: 10.1016/j.stem.2022.04.004
Alsat, E. et al. Hypoxia impairs cell fusion and differentiation process in human cytotrophoblast, in vitro. J. Cell. Physiol. 168, 346–353 (1996).
pubmed: 8707870
doi: 10.1002/(SICI)1097-4652(199608)168:2<346::AID-JCP13>3.0.CO;2-1
Nelson, D. M., Johnson, R. D., Smith, S. D., Anteby, E. Y. & Sadovsky, Y. Hypoxia limits differentiation and up-regulates expression and activity of prostaglandin H synthase 2 in cultured trophoblast from term human placenta. Am. J. Obstet. Gynecol. 180, 896–902 (1999).
pubmed: 10203658
doi: 10.1016/S0002-9378(99)70661-7
Io, S. et al. Capturing human trophoblast development with naive pluripotent stem cells in vitro. Cell Stem Cell 28, 1023-1039.e13 (2021).
pubmed: 33831365
doi: 10.1016/j.stem.2021.03.013
Rostovskaya, M., Andrews, S., Reik, W. & Rugg-Gunn, P. J. Amniogenesis occurs in two independent waves in primates. Cell Stem Cell 29, 744-759.e6 (2022).
pubmed: 35439430
pmcid: 9627701
doi: 10.1016/j.stem.2022.03.014
Lippmann, E. S. et al. Deterministic HOX patterning in human pluripotent stem cell-derived neuroectoderm. Stem Cell Rep. 4, 632–644 (2015).
doi: 10.1016/j.stemcr.2015.02.018
Wobus, A. M. et al. Retinoic acid accelerates embryonic stem cell-derived cardiac differentiation and enhances development of ventricular cardiomyocytes. J. Mol. Cell. Cardiol. 29, 1525–1539 (1997).
pubmed: 9220339
doi: 10.1006/jmcc.1997.0433
Lippmann, E. S., Al-Ahmad, A., Azarin, S. M., Palecek, S. P. & Shusta, E. V. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources. Sci. Rep. 4, 1–10 (2014).
doi: 10.1038/srep04160
Gudas, L. J. & Wagner, J. A. Retinoids regulate stem cell differentiation. J. Cell. Physiol. 226, 322–330 (2011).
pubmed: 20836077
pmcid: 3315372
doi: 10.1002/jcp.22417
Cabezas-Wallscheid, N. et al. Vitamin A-retinoic acid signaling regulates hematopoietic stem cell dormancy. Cell 169, 807-823.e19 (2017).
pubmed: 28479188
doi: 10.1016/j.cell.2017.04.018
Tang, X. H. & Gudas, L. J. Retinoids, retinoic acid receptors, and cancer. Annu. Rev. Pathol. Mech. Dis. 6, 345–364 (2011).
doi: 10.1146/annurev-pathol-011110-130303
Cheng, T. et al. CHIR99021 combined with retinoic acid promotes the differentiation of primordial germ cells from human embryonic stem cells. Oncotarget 8, 7814–7826 (2017).
pubmed: 27999196
doi: 10.18632/oncotarget.13958
Yabe, S. et al. Comparison of syncytiotrophoblast generated from human embryonic stem cells and from term placentas. Proc. Natl. Acad. Sci. USA 113, E2598–E2607 (2016).
pubmed: 27051068
pmcid: 4868474
doi: 10.1073/pnas.1601630113
Ye, L. et al. Effective cardiac myocyte differentiation of human induced pluripotent stem cells requires VEGF. PLoS ONE 8, (2013).
Johnson, W. E., Li, C. & Rabinovic, A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 8, 118–127 (2007).
pubmed: 16632515
doi: 10.1093/biostatistics/kxj037
Zhang, Y., Parmigiani, G. & Johnson, W. E. ComBat-seq: Batch effect adjustment for RNA-seq count data. NAR Genomics Bioinforma. 2, lqaa078 (2020).
doi: 10.1093/nargab/lqaa078
Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010).
pubmed: 19910308
doi: 10.1093/bioinformatics/btp616
McCarthy, D. J., Chen, Y. & Smyth, G. K. Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res. 40, 4288–4297 (2012).
pubmed: 22287627
pmcid: 3378882
doi: 10.1093/nar/gks042
Chen, Y., Lun, A. T. L. & Smyth, G. K. From reads to genes to pathways: differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline. F1000Research 5 (2016).
Chen, Y., Chen, L., Lun, A. T. L., Baldoni, P. L. & Smyth, G. K. EdgeR 40: powerful differential analysis of sequencing data with expanded functionality and improved support for small counts and larger datasets. BioRxiv. https://doi.org/10.1101/2024.01.21.576131 (2024).
doi: 10.1101/2024.01.21.576131
pubmed: 39091884
pmcid: 11291146