Depletion of aneuploid cells in human embryos and gastruloids

Nature Cell Biology, Journal Year: 2021, Volume and Issue: 23(4), P. 314 - 321

Published: April 1, 2021

Language: Английский

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Control of stem cell renewal and fate by YAP and TAZ

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(12), P. 895 - 911

Published: Aug. 25, 2023

Language: Английский

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The Hippo signaling pathway in development and regeneration

Cell Reports, Journal Year: 2024, Volume and Issue: 43(3), P. 113926 - 113926

Published: March 1, 2024

The Hippo signaling pathway is a central growth control mechanism in multicellular organisms. By integrating diverse mechanical, biochemical, and stress cues, the orchestrates proliferation, survival, differentiation, mechanics of cells, which turn regulate organ development, homeostasis, regeneration. A deep understanding regulation function therefore holds great promise for developing novel therapeutics regenerative medicine. Here, we provide updates on molecular organization mammalian network, review regulatory signals functional outputs pathway, discuss roles development

Language: Английский

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Regulation of human trophoblast gene expression by endogenous retroviruses

Nature Structural & Molecular Biology, Journal Year: 2023, Volume and Issue: 30(4), P. 527 - 538

Published: April 1, 2023

The placenta is a fast-evolving organ with large morphological and histological differences across eutherians, but the genetic changes driving placental evolution have not been fully elucidated. Transposable elements, through their capacity to quickly generate variation affect host gene regulation, may helped define species-specific trophoblast expression programs. Here we assess contribution of transposable elements human as enhancers or promoters. Using epigenomic data from primary stem-cell lines, identified multiple endogenous retrovirus families regulatory potential that lie close genes preferential in trophoblast. These largely primate-specific are associated inter-species bound by transcription factors key roles development. editing, demonstrate several act transcriptional important genes, such CSF1R PSG5. We also identify an LTR10A element regulates ENG expression, affecting secretion soluble endoglin, implications for preeclampsia. Our show transposons made contributions suggest activity pregnancy outcomes.

Language: Английский

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TEAD4 ensures postimplantation development by promoting trophoblast self-renewal: An implication in early human pregnancy loss

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(30), P. 17864 - 17875

Published: July 15, 2020

Significance Reproductive success in placental mammals relies on proper development of the trophoblast lineage. In particular, a balance self-renewal vs. differentiation progenitors is critical for establishment pregnancy. A defect this process causes early pregnancy loss. Here, we showed that Hippo signaling effector, TEAD4, essential progenitor postimplantation mammalian embryos. Using genetic mouse models and human TSCs, including TSCs from patients with recurrent losses, identified TEAD4-dependent, evolutionarily conserved gene expression program promotes stemness cell proliferation ensures utero survival developing fetus.

Language: Английский

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Hippo pathway: Regulation, deregulation and potential therapeutic targets in cancer

Cancer Letters, Journal Year: 2021, Volume and Issue: 507, P. 112 - 123

Published: March 18, 2021

Language: Английский

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Characterization of primary models of human trophoblast

Development, Journal Year: 2021, Volume and Issue: 148(21)

Published: Oct. 15, 2021

ABSTRACT Two recently developed models, trophoblast organoids and stem cells (TSCs), are useful tools to further the understanding of human placental development. Both differentiate from villous cytotrophoblast (VCT) either extravillous (EVT) or syncytiotrophoblast (SCT). Here, we compare transcriptomes miRNA profiles these models identify which they resemble in vivo. Our findings indicate that TSCs do not readily undergo SCT differentiation closely at base cell columns where EVT derives. In contrast, similar VCT spontaneous differentiation. A defining feature is leukocyte antigen (HLA) null, whereas expresses HLA-C, -G -E molecules. We find retain vivo characteristics. express classical HLA-A HLA-B molecules, maintain their expression after differentiation, with upregulation HLA-G. Furthermore, HLA differs when grown 3D rather than 2D, suggesting mechanical cues important. results can be used select most suitable model for study development, function pathology.

Language: Английский

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Two distinct trophectoderm lineage stem cells from human pluripotent stem cells

Journal of Biological Chemistry, Journal Year: 2021, Volume and Issue: 296, P. 100386 - 100386

Published: Jan. 1, 2021

The trophectoderm layer of the blastocyst-stage embryo is precursor for all trophoblast cells in placenta. Human stem (TS) have emerged as an attractive tool studies on early development. However, use TS cell models constrained by limited genetic diversity existing lines and restrictions using human fetal tissue or embryos needed to generate additional lines. Here we report derivation two distinct types lineage from pluripotent cells. Analogous villous cytotrophoblasts vivo, first a CDX2- comparable with placenta-derived cells—they both exhibit identical expression key markers, are maintained culture differentiate under similar conditions, share high transcriptome similarity. second CDX2+ requirements, differences gene differentiation, relative Derivation will significantly enable construction vitro normal pathological placental Specification inner mass differentiation event during embryonic mediates blastocyst implantation uterus Upon implantation, forms cytotrophoblast (CTB), putative that can form major placenta, extravillous (EVT) syncytiotrophoblast (STB) (1Bischof P. Irminger-Finger I. cytotrophoblastic cell, mononuclear chameleon.Int. J. Biochem. Cel. Biol. 2005; 37: 1-16Crossref PubMed Scopus (125) Google Scholar, 2Benirschke Kurt. Baergen R.N. Burton G. Graham Pathology Placenta [electronic Resource]. Springer, Heidelberg2012Crossref (48) Scholar). EVTs involved remodeling uterine arteries, which critical ensure adequate perfusion placenta maternal blood, whereas multinucleated STB nutrient gas exchange at maternal–fetal interface (3Yabe S. Alexenko A.P. Amita M. Yang Y. Schust D.J. Sadovsky Ezashi T. Roberts R.M. Comparison generated term placentas.Proc. Natl. Acad. Sci. U. A. 2016; 113: E2598-E2607Crossref (68) 4Moser Orendi K. Gauster Siwetz Helige C. Huppertz B. art identification trophoblast.Placenta. 2011; 32: 197-199Crossref (29) Abnormalities development associated pregnancy-related pathologies such miscarriage, preeclampsia, accreta. Yet, despite its relevance health, constraints research impede mechanistic insight into Trophoblast derived first-trimester samples model system (5Okae H. Toh Sato Hiura Takahashi Shirane Kabayama Suyama Sasaki Arima cells.Cell cell. 2018; 22: 50-63.e6Abstract Full Text PDF (233) restricted accessibility gestation low limit this model. In contrast, (hPSCs) more accessible source generating trophoblast. Of importance, unlike primary where projected pregnancy outcome uncertain, induced (hiPSCs) potentially provide validated (6Sheridan M.A. Jain Lyons A.S. Brahmasani S.R. Dai Tian Ellersieck M.R. Tuteja Schulz L.C. Early onset preeclampsia trophoblast.Proc. 2019; 116: 4336-4345Crossref (20) whether bona fide be obtained hPSCs has been subject intense debate (7Roberts Loh K.M. Bernardo Adachi Telugu B.P.V.L. Pedersen R.A. Differentiation cells: To not be?.Reproduction (Cambridge, England). 2014; 147: D1-D12Crossref (45) A rigorous head-to-head comparison between their vivo counterparts proven difficult owing multiple reasons. Previous used varying experimental protocols (8Roberts Sheridan exposed BMP4†.Biol. Reprod. 99: 212-224Crossref (22) Scholar); cultures terminally differentiated heterogeneity contain many types, until recently self-renewing TS-like had (9Dong Beltcheva Gontarz Zhang Popli Fischer L.A. Khan S.A. Park K.-M. Yoon E.-J. Xing X. Kommagani R. Wang Solnica-Krezel L. Theunissen T.W. naïve cells.eLife. 2020; 9: e52504Crossref (57) 10Cinkornpumin J.K. Kwon S.Y. Guo Hossain Sirois Russett C.S. Tseng H.W. Okae Duchaine T.F. Liu W. Pastor W.A. Naive give rise trophoblast-like Methylome.Stem Cell Rep. 15: 198-213Abstract (33) 11Li Z. Kurosawa O. Iwata Development cystic structures limited-area culture.Biochem. Biophysical Res. Commun. 505: 671-676Crossref (5) 12Gao Nowak-Imialek Chen D. Herrmann Ruan A.C.H. Eckersley-Maslin Ahmad Lee Y.L. Kobayashi Ryan Zhong Zhu Wu et al.Establishment porcine expanded potential cells.Nat. 21: 687-699Crossref (120) study, maintenance hPSCs, specifically (hESCs) hiPSCs, chemically defined conditions. early-gestation CTB. type Critically, isolation populations allowed direct hPSCs; genome-wide transcriptomic analysis functional assays demonstrate very similarity placenta- hPSC-derived routine powerful tools Media formulations previous hESCs included components knockout serum replacement (KSR) bovine albumin (BSA) act carriers lipids. Albumin-associated lipids implicated activation G-protein–coupled receptor–mediated signaling (13Yu F.-X. Zhao Panupinthu N. Jewell J.L. Lian L.H. Yuan Tumaneng Li Fu X.-D. Mills G.B. Guan K.-L. Regulation Hippo-YAP pathway G-protein-coupled receptor signaling.Cell. 2012; 150: 780-791Abstract (974) 14Mendelson Evans Hla Sphingosine 1-phosphate signalling.Development 141: 5-9Crossref (165) For instance, phospholipid sphingosine-1 phosphate (S1P) present KSR activate YAP signaling. plays role specification mouse (15Yagi Kohn M.J. Karavanova Kaneko K.J. Vullhorst DePamphilis M.L. Buonanno Transcription factor TEAD4 specifies beginning mammalian development.Development 2007; 134: 3827-3836Crossref (353) 16Knott J.G. Paul Transcriptional regulators mammals hemochorial placentation.Reproduction 148: R121-R136Crossref (40) 17Nishioka Yamamoto Kiyonari Sawada Ota Nakao Tead4 required pre-implantation embryos.Mech. Dev. 2008; 125: 270-283Crossref (331) Scholar), well (18Saha Ganguly Home Bhattacharya Ray Ghosh Rumi M.A.K. Marsh French V. Gunewardena ensures postimplantation promoting self-renewal: An implication loss.Proc. 117: 202002449Crossref 19Meinhardt Haider Kunihs Saleh Pollheimer Fiala Hetey Feher Szilagyi Than N.G. Knöfler Pivotal transcriptional co-activator stemness developing placenta.Proc. 13562-13570Crossref (25) We investigated S1P context modifying our protocol utilized (20Sarkar Randall S.M. Collier T.S. Nero Russell T.A. Muddiman D.C. Rao B.M. Activin/nodal Switches terminal fate cell-derived trophoblasts.J. Chem. 2015; 290: 8834-8848Abstract (15) 21Sarkar Mischler Dorman K.F. Boggess K.A. Identification epigenetic proteins expressed trophoblasts Proteome 2433-2444Crossref (6) H1 H9 cultured E8 medium were 6 days E7 (E8 without transforming growth factor-beta1 [TGFβ1]) supplemented S1P, treatment BMP4 activin/nodal inhibitor SB431542 (Fig. 1A). Under these observed upregulation marker CDX2 CTB ELF5 S1, B). Upregulation TBX4 was after days. overall there no significant changes markers neural mesodermal suggesting lineages did occur Immunofluorescence day confirmed pan-trophoblast KRT7, P63 GATA3; (Figs. 1B S1C). ability STB, those previously employed formation mesenchymal epithelial over 6-day period when passaged epidermal (EGF) SB431542. showed KRT7 EVT VE-Cadherin HLA-G 1C, S1D). Alternatively, passaging CTB-like E6 TGFβ1 fibroblast factor-2 [FGF2]) activin EGF resulted KRT7+ multinucleate expressing hCG syncytin 8-day 1D, S1E). Removal hESC abolished express 1E, S2A) conditions also absence evidenced lack 1F, S2B). Also, downregulation transcripts mesoderm upon removal S2C). Taken together results show cells, utilizing complex containing S1P. Furthermore, addition exogenous necessary medium. Rho GTPase signaling, downstream receptors activated nuclear localization (22Ohgushi Minaguchi Sasai Rho-signaling-directed YAP/TAZ activity Underlies long-term Survival Expansion 17: 448-461Abstract (100) 23Mo J.-S. Yu Gong Brown J.H. protease-activated (PARs).Genes 26: 2138-2143Crossref (195) Both Rho/RhoA kinase (ROCK) play (24Nishioka Inoue Ralston Yabuta Hirahara Stephenson R.O. Ogonuki Makita Kurihara Morin-Kensicki E.M. Nojima Rossant al.The Hippo Lats Yap pattern distinguish mass.Dev. 2009; 16: 398-410Abstract (657) 25Kono Tamashiro D.A.A. Alarcon V.B. Inhibition RHO-ROCK enhances ICM suppresses TE characteristics through blastocyst.Dev. 394: 142-155Crossref (79) Therefore, Rho/ROCK hESCs. Y-27632 subsequent investigate hESCs; however, weak only few S3A). On other hand, addition, presence ROCK inhibition formation, shown S3B). hESCs, line (H9) expresses inducible shRNA against (H9-YAP-ishRNA) scrambled control (26Hsiao Lampe Nillasithanukroh Han Palecek S.P. density modulates signaling.Biotechnol. 11: 662-675Crossref (26) knockdown relevant markers. It notable death S3, Gene revealed reduction knockdown, S3C). Significant genes LMO2 observed, T upregulated, H9-YAP-ishRNA, control. together, acts receptor-mediated receptor-independent pathways (14Mendelson 27Maceyka Harikumar K.B. Milstien Spiegel Sphingosine-1-phosphate disease.Trends 50-60Abstract (695) specific mechanism action trophoblast, replaced D-erythro-dihydrospingosine-1-phosphate (dhS1P) protocol. dhS1P agonist (S1PRs) but does mediate intracellular effect (28Van Brocklyn J.R. M.-J. Menzeleev Olivera Edsall Cuvillier Thomas D.M. Coopman P.J.P. Thangada C.H. Dual actions sphingosine-1-phosphate: Extracellular G i -coupled Edg-1 regulate proliferation Survival.J. 1998; 142: 229-240Crossref (444) Replacing yielded results—CTB-like CDX2, GATA3, P63, 2A S4A). further described 1A), hCG, 2, B C; Fig. S4, C). These suggest S1PR extracellularly S1PR1-5 TBs S1PR1-3 (29Johnstone E.D. Chan Sibley C.P. Davidge S.T. Lowen Guilbert L.J. G(i)-coupled response.J. lipid 46: 1833-1839Abstract (34) selective chemical agonists S1PR1-3—CYM5442 hydrochloride, CYM5520, CYM5541, respectively—to replace discussed. Expression three Similarly, each some variability S5). S1PR2 strong cytoplasmic staining agonists. Formation large pronounced S1PR3 used, compared S1PR1 agonist. enhanced EVTs, effects system. Since qualitative observations could chose studies. CYM5541 blastocyst- plating (TSCM) developed al. hESC-derived underwent colonies retained single passage. upregulated little 2 initiation decreases reported CDX2+/p63+ BMP 4 (30Horii Wakeland A.K. Pizzo D.P. Nelson K.K. Sabatini Laurent Parast M.M. disease.Proc. United States America. E3882-E3891Crossref (66) explored shorter step obtaining 3A). After 3 uniformly 3B). most lose 3C). Quantitative image nearly 3, contrast 6. note, reduced fraction case 3-day protocol; 3D). Transcriptome RNA sequencing identified 291 higher levels 330 lower versus undifferentiated (Tables S1 S2).Expression trophectoderm-associated HAND1, TFAP2A, pluripotency-associated NANOG downregulated. set enrichment differentially 567 202 ontology (GO) categories (of 9996 queried categories) respectively S3 S4). Consistent GO terms epithelium development, proliferation, four (denoted TM4), GSK3β CHIR99021, TGFβ A83-01, FGF10. CHIR99021 A83-01 TSCM cells; FGF10 because FGFR2b active Cells TM4 30+ passages course 5 months. medium, TFAP2C, YAP, TEAD4, GATA3 3E S6) 31Choi Carey Wilson C.A. Knott AP-2γ core regulator tight junction biogenesis cavity embryogenesis.Development 139: 4623-4632Crossref 32Home Saha Dutta Yoo Pal Vivian Larson Petroff Gallagher P.G. V.P. White K.L. Golos T.G. Behr al.Altered subcellular transcription regulates commitment.Proc. 109: 7362-7367Crossref (113) 33Ralston Cox B.J. Nishioka Chea E. Rugg-Gunn Robson Draper J.S. Gata3 parallel Cdx2.Development 2010; 137: 395-403Crossref (299) 34Niwa Toyooka Shimosato Strumpf Yagi Interaction Oct3/4 Cdx2 determines differentiation.Cell. 123: 917-929Abstract (854) P63. strongly lost once villi formed 35Hemberger Udayashankar Tesar Moore G.J. ELF5-enforced networks define epigenetically regulated compartment placenta.Hum. Mol. Genet. 19: 2456-2467Crossref (126) 36Blakeley Fogarty N.M.E. del Valle Wamaitha S.E. Hu T.X. Elder Snell Christie Niakan Defining single-cell RNA-seq.Development. 3151-3165Crossref (262) 37Knöfler Gamage T.K.J.B. James development: Key molecular mechanisms systems.Cell Life 76: 3479-3496Crossref (144) indicate do denoted hPSC-TSCDX2 evaluated same able 3F). treatment, elongated acquired flattened morphology. passage, minimal 3G). morp

Language: Английский

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WNT and NOTCH signaling in human trophoblast development and differentiation

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(6)

Published: May 13, 2022

Abstract Correct development of the human placenta and its differentiated epithelial cells, syncytial trophoblasts (STBs) extravillous (EVTs), is crucial for a successful pregnancy outcome. STBs develop by cell fusion mononuclear cytotrophoblasts (CTBs) in placental floating villi, whereas migratory EVTs originate from specialized villi anchoring to maternal decidua. Defects trophoblast differentiation have been associated with severe disorders such as early-onset preeclampsia fetal growth restriction. However, evolutionary pathways underlying normal adverse placentation are poorly understood. Herein, we discuss Wingless (WNT) NOTCH signaling, two that play pivotal roles development. Whereas WNT necessary expansion progenitors stem NOTCH1 required proliferation survival EVT precursors. Differentiation latter orchestrated switch receptor expression well changes ligands their downstream effectors.

Language: Английский

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How trophoblasts fuse: an in-depth look into placental syncytiotrophoblast formation

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(8)

Published: July 20, 2022

Language: Английский

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