Lysophosphatidic Acid Accelerates Bovine In Vitro-Produced Blastocyst Formation through the Hippo/YAP Pathway

Yu, Bo; Tol, Helena T A van; Oei, Christine; Stout, T.A.E.; Roelen, Bernard A. J.

doi:10.3390/ijms22115915

Cited by 10 publications

(4 citation statements)

References 38 publications

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“…Additionally, data derived from our time-lapse experiments show that within the same culture wells TE cysts expand faster in twin blastoids than in singleton blastoids (linear regression, P < 0.0001, Figure S1H, Supporting Information). Given that LPA has been reported to accelerate in vitro blastocyst formation in bovines [33] and we indeed see an increase in cyst diameter in response to increasing LPA concentrations (Kruskal-Wallis test, P < 0.0001, Figure S1I, Supporting Information), we suspected that accelerated TE expansion may drive the ICM splitting in our system. This is further supported by the finding that delaying TE induction by 24 h decreased twin blastoid formation (Student's t-test, P = 0.019, Figure S1J, Supporting Information).…”

Section: Te Expansion Drives Icm Divisionmentioning

confidence: 82%

Monochorionic Twinning in Bioengineered Human Embryo Models

Luijkx,

Ak,

Guo

et al. 2024

Advanced Materials

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Monochorionic twinning of human embryos increases the risk of complications during pregnancy. The rarity of such twinning events, combined with ethical constraints in human embryo research, makes investigating the mechanisms behind twinning practically infeasible. As a result, there is a significant knowledge gap regarding the origins and early phenotypic presentation of monochorionic twin embryos. In this study, a microthermoformed‐based microwell screening platform is used to identify conditions that efficiently induce monochorionic twins in human stem cell‐based blastocyst models, termed “twin blastoids”. These twin blastoids contain a cystic GATA3+ trophectoderm‐like epithelium encasing two distinct inner cell masses (ICMs). Morphological and morphokinetic analyses reveal that twinning occurs during the cavitation phase via splitting of the OCT4+ pluripotent core. Notably, each ICM in twin blastoids contains its own NR2F2+ polar trophectoderm‐like region, ready for implantation. This is functionally tested in a microfluidic chip‐based implantation assay with epithelial endometrium cells. Under defined flow regimes, twin blastoids show increased adhesion capacity compared to singleton blastoids, suggestive of increased implantation potential. In conclusion, the development of technology enabling large‐scale formation of twin blastoids, coupled with high‐sensitivity readout capabilities, presents an unprecedented opportunity for systematically exploring monochorionic twin formation and its impact on embryonic development.This article is protected by copyright. All rights reserved

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Section: Te Expansion Drives Icm Divisionmentioning

confidence: 82%

Monochorionic Twinning in Bioengineered Human Embryo Models

Luijkx,

Ak,

Guo

et al. 2024

Advanced Materials

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“…Studies have reported that Hippo-YAP signaling is important for the activation of nuclear transcription factor CDX2 expression in mouse embryos [ 30 , 31 ]. Meanwhile, CDX2 is preferentially expressed in GC [ 32 , 33 ].…”

Section: Resultsmentioning

confidence: 99%

LncRNA H19-rich extracellular vesicles derived from gastric cancer stem cells facilitate tumorigenicity and metastasis via mediating intratumor communication network

et al. 2023

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Background Extracellular vesicles (EVs) transport biologically active molecules, and represent a recently identified way of intercellular communication. Recent evidence has also reported that EVs shed by cancer stem cells (CSCs) make a significant contribution to carcinogenesis and metastasis. Here, this study aims to explore the possible molecular mechanism of CSCs-EVs in gastric cancer (GC) by mediating intratumor communication network. Methods CSCs and non-stem cancer cells (NSCCs) were sorted from GC cells, and EVs were isolated from CSCs. H19 was knocked down in CSCs, and CSCs-EVs or CSCs-EVs containing shRNA-H19 (CSCs-EVs-sh-H19) were co-cultured with NSCCs, followed by evaluation of the malignant behaviors and stemness of NSCCs. Mouse models of GC were established and injected with CSCs-EVs from sh-H19-treated NSCCs in vivo. Results CSCs had notable self-renewal and tumorigenic capacity compared with NSCCs. CSCs promoted the malignant behaviors of NSCCs and expression of stemness marker proteins through secretion of EVs. Inhibited secretion of CSCs-EVs curtailed the tumorigenicity and metastasis of NSCCs in vivo. H19 could be delivered by CSCs-EVs into NSCCs. H19 promoted the malignant behaviors of NSCCs and stemness marker protein expression in vitro along with tumorigenicity and liver metastasis in vivo, which was mechanistically associated with activation of the YAP/CDX2 signaling axis. Conclusion Taken together, the present study points to the importance of a novel regulatory axis H19/YAP/CDX2 in carcinogenic and metastatic potential of CSCs-EVs in GC, which may be potential targets for anticancer therapy.

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“…Immunofluorescence was performed according to Yu et al [79] with some modifications. The embryos were fixed in 4% paraformaldehyde for 1 h at 4 • C. Subsequently, the embryos were permeated with 0.5% Triton X-100 (Sigma-Aldrich, St. Louis, MO, USA) at room temperature for 40 min.…”

Section: Immunofluorescence Staining Of Embryomentioning

confidence: 99%

Effects of Regulating Hippo and Wnt on the Development and Fate Differentiation of Bovine Embryo

Zhang,

et al. 2024

IJMS

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The improvement of in vitro embryo development is a gateway to enhance the output of assisted reproductive technologies. The Wnt and Hippo signaling pathways are crucial for the early development of bovine embryos. This study investigated the development of bovine embryos under the influence of a Hippo signaling agonist (LPA) and a Wnt signaling inhibitor (DKK1). In this current study, embryos produced in vitro were cultured in media supplemented with LPA and DKK1. We comprehensively analyzed the impact of LPA and DKK1 on various developmental parameters of the bovine embryo, such as blastocyst formation, differential cell counts, YAP fluorescence intensity and apoptosis rate. Furthermore, single-cell RNA sequencing (scRNA-seq) was employed to elucidate the in vitro embryonic development. Our results revealed that LPA and DKK1 improved the blastocyst developmental potential, total cells, trophectoderm (TE) cells and YAP fluorescence intensity and decreased the apoptosis rate of bovine embryos. A total of 1203 genes exhibited differential expression between the control and LPA/DKK1-treated (LD) groups, with 577 genes upregulated and 626 genes downregulated. KEGG pathway analysis revealed significant enrichment of differentially expressed genes (DEGs) associated with TGF-beta signaling, Wnt signaling, apoptosis, Hippo signaling and other critical developmental pathways. Our study shows the role of LPA and DKK1 in embryonic differentiation and embryo establishment of pregnancy. These findings should be helpful for further unraveling the precise contributions of the Hippo and Wnt pathways in bovine trophoblast formation, thus advancing our comprehension of early bovine embryo development.

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Lysophosphatidic Acid Accelerates Bovine In Vitro-Produced Blastocyst Formation through the Hippo/YAP Pathway

Cited by 10 publications

References 38 publications

Monochorionic Twinning in Bioengineered Human Embryo Models

Monochorionic Twinning in Bioengineered Human Embryo Models

LncRNA H19-rich extracellular vesicles derived from gastric cancer stem cells facilitate tumorigenicity and metastasis via mediating intratumor communication network

Effects of Regulating Hippo and Wnt on the Development and Fate Differentiation of Bovine Embryo

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