MicroRNA regulation of murine trophoblast stem cell self-renewal and differentiation

Saha, Sarbani; Ain, Rupasri

doi:10.26508/lsa.202000674

Cited by 13 publications

(25 citation statements)

References 38 publications

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“…MicroRNA have been shown to play an important role in every step of a successful pregnancy including trophectoderm development, implantation and placentation [1]. Cytotrophoblast differentiation towards both the syncytial and extravillous pathways have been shown to be regulated by multiple miRNAs [1,2,5,[39][40][41]. Previous studies have reported that miR-210-3p inhibits trophoblast invasion [4,18,19].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of miR-210-3p Impairs Extravillous Trophoblast Functions Associated with Uterine Spiral Artery Remodeling

Hayder

Nadeem

et al. 2021

IJMS

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Hsa-miR-210-3p has been reported to be upregulated in preeclampsia (PE); however, the functions of miR-210-3p in placental development are not fully understood, and, consequently, miR-210-3p’s role in the pathogenesis of PE is still under investigation. In this study, we found that overexpression of miR-210-3p reduced trophoblast migration and invasion, extravillous trophoblast (EVT) outgrowth in first trimester explants, expression of endovascular trophoblast (enEVT) markers and the ability of trophoblast to form endothelial-like networks. In addition, miR-210-3p overexpression significantly downregulated the mRNA levels of interleukin-1B and -8, as well as CXC motif ligand 1. These cytokines have been suggested to play a role in EVT invasion and the recruitment of immune cells to the spiral artery remodeling sites. We also showed that caudal-related homeobox transcription factor 2 (CDX2) is targeted by miR-210-3p and that CDX2 downregulation mimicked the observed effects of miR-210-3p upregulation in trophoblasts. These findings suggest that miR-210-3p may play a role in regulating events associated with enEVT functions and its overexpression could impair spiral artery remodeling, thereby contributing to PE.

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Section: Discussionmentioning

confidence: 99%

Overexpression of miR-210-3p Impairs Extravillous Trophoblast Functions Associated with Uterine Spiral Artery Remodeling

Hayder

Nadeem

et al. 2021

IJMS

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“… 25 , 26 , 27 , 28 , 29 On the other hand, CDX2 is also important for maintaining the stemness of mouse trophoblasts for correct placental formation, and this CDX2 expression is induced by epiblast‐derived FGF4 via the MEK‐ERK signaling pathway. 30 , 31 , 32 , 33 Especially, we previously reported that the abnormal expression of Cdx2 after differentiation disrupts the expression of some differentiation marker genes in mouse androgenetic embryo‐derived trophoblast stem cells (AG‐TSCs). 34 Thus, CDX2 possesses dual functions (specification of TE and maintenance of trophoblast stemness) for the morphogenesis of extraembryonic tissues.…”

Section: Introductionmentioning

confidence: 99%

CDX2 downregulation in mouse mural trophectoderm during peri‐implantation is heteronomous, dependent on the YAP‐TEAD pathway and controlled by estrogen‐induced factors

Suzuki

Okura

Nagakura

et al. 2022

Reprod Medicine & Biology

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Purpose To investigate the transition of CDX2 expression patterns in mouse trophectoderm (TE) and its regulatory mechanisms during implantation. Methods Mouse E3.5–4.5 blastocysts were used to immunostain CDX2, YAP, TEAD4, and ESRRB. Endogenous estrogen signaling was perturbed by administrating estrogen receptor antagonist ICI 182,780 or ovariectomy followed by administration of progesterone and β‐estradiol to elucidate the relationship between the transition of CDX2 expression patterns and ovarian estrogen‐dependent change in the uterine environment. Results CDX2 expression was gradually downregulated in the mural TE from E4.0 in vivo , whereas CDX2 downregulation was not observed in blastocysts cultured in KSOM. Fetal bovine serum (FBS) supplementation in KSOM induced CDX2 downregulation independently of blastocyst attachment to dishes. CDX2 downregulation in the mural TE was repressed by administration of ICI 182,780 or by ovariectomy, and administration of β‐estradiol into ovariectomized mice retriggered CDX2 downregulation. Furthermore, Cdx2 expression in the mural TE might be controlled by the YAP‐TEAD pathway. Conclusions CDX2 downregulation was induced heteronomously in the mural TE from E4.0 by uterus‐derived factors, the secretion of which was stimulated by ovarian estrogen.

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“…2 E). CDX2 is known to transactivate CYCLIN D1 in TSCs [ 43 ]. Therefore, to understand YAP-reliant self-renewal of TSCs, Cyclin D1 transcript and protein levels were assessed in TSCs in YAP knocked down and overexpressed conditions.…”

Section: Resultsmentioning

confidence: 99%

“…BrdU incorporation assay was performed as described previously [ 43 ] and is detailed in Additional file 1 .…”

Section: Methodsmentioning

confidence: 99%

Molecular regulation of trophoblast stem cell self-renewal and giant cell differentiation by the Hippo components YAP and LATS1

Basak

Ain

2022

Stem Cell Res Ther

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Background Trophoblast stem cells (TSCs), the precursors of trophoblast cells of placenta, possess the potential to differentiate into various trophoblastic subtypes in vitro. Establishment of extraembryonic trophoblastic lineage is preceded by the “outside versus inside” positional information in preimplantation embryos, critically synchronized by the Hippo components. Abundant expression of Hippo effector YAP in TSCs and differentiated cells with paucity of information on Hippo regulation of TSC proliferation/differentiation led us test the hypothesis that Hippo dynamics is one of the regulators of TSC proliferation/differentiation. Methods Blastocyst-derived murine TSCs were used. Dynamics of Hippo components were analyzed using immunofluorescence, western blotting, immunoprecipitation, qRT-PCR. Interaction studies were performed using full-length and deletion constructs. BrdU incorporation assay, flow cytometry-based polyploidy analysis and confocal microscopy were used to decipher the underlying mechanism. Results YAP translocates to the nucleus in TSCs and utilizes its WW2 domain to interact with the PPQY motif of the stemness factor, CDX2. YAP limits TSC proliferation with associated effect on CDX2 target CyclinD1. Trophoblast giant cells (TGC) differentiation is associated with cytoplasmic retention of YAP, heightened pYAPSer127, decrease in the level of the core Hippo component, LATS1, which thereby impedes LATS1-LIMK2 association. Decreased LATS1-LIMK2 complex formation in TGCs was associated with elevated pLIMK2Thr505 as well as its target pCOFILINSer3. Precocious overexpression of LATS1 during trophoblast differentiation decreased TGC marker, Prl2c2, diminished pLIMK2Thr505 and inactive COFILIN (pCOFILINSer3) while COFILIN-phosphatase, CHRONOPHIN remained unchanged. LATS1 overexpression inhibited trophoblast endoreduplication with smaller-sized TGC-nuclei, lower ploidy level and disintegrated actin filaments. Inhibition of LIMK2 activity recapitulated the effects of LATS1 overexpression in trophoblast cells. Conclusion These results unveil a multilayered regulation of trophoblast self-renewal and differentiation by the Hippo components.

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MicroRNA regulation of murine trophoblast stem cell self-renewal and differentiation

Cited by 13 publications

References 38 publications

Overexpression of miR-210-3p Impairs Extravillous Trophoblast Functions Associated with Uterine Spiral Artery Remodeling

Overexpression of miR-210-3p Impairs Extravillous Trophoblast Functions Associated with Uterine Spiral Artery Remodeling

CDX2 downregulation in mouse mural trophectoderm during peri‐implantation is heteronomous, dependent on the YAP‐TEAD pathway and controlled by estrogen‐induced factors

Molecular regulation of trophoblast stem cell self-renewal and giant cell differentiation by the Hippo components YAP and LATS1

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