CDX2 is essential for cell proliferation and polarity in porcine blastocysts

Bou, Gerelchimeg; Liu, Shichao; Sun, Mingwei; Zhu, Jiang; Xue, Binghua; Guo, Jia; Zhao, Yueming; Qu, Bo; Weng, Xiaogang; Wei, Yanchang; Lei, Lei

doi:10.1242/dev.141085

Cited by 67 publications

(63 citation statements)

References 56 publications

(95 reference statements)

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“…The morula group showed expression of OCT4 ( POU5F1 ), SOX2 , and KLF4 , but not NANOG , while early blastocyst (EB) cells segregated into two lineages: ICM cells expressing NANOG and SOX2 , and TE cells with GATA2 , GATA3 , and DAB2 . Expression of CDX2 was seen in a few TE cells at this early stage 15,18 , but OCT4 expression was seen in all cells, consistent with observations in human and monkey blastocysts 2,19 . There was evident expression of pluripotency genes; SOX15 , KLF4 and KLF17 in the ICM and EPI, as in human epiblast cells.…”

Section: Resultssupporting

confidence: 89%

Lineage segregation, pluripotency and X-chromosome inactivation in the pig pre-gastrulation embryo

Ramos‐Ibeas

Sang²,

Zhu

et al. 2018

Preprint

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5High-resolution molecular programs delineating the cellular foundations of and then of epiblast and hypoblast in late blastocysts. We detected distinct 3 3 pluripotent states, first as a short 'naïve' state followed by a protracted primed state. comprehending early human development and a foundation for further studies of 3 7 human pluripotent stem cell differentiation in pig interspecies chimeras. . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/347823 doi: bioRxiv preprint first posted online Jun. 20, 2018; 3 Pre-gastrulation embryo development shows broad similarities between mammals, although 4 0 species-specific differences in early lineage segregation, the establishment of pluripotency, 4 1 and X chromosome inactivation have been reported [1][2][3] . Mouse embryos, which are widely 4 2 used as a model for mammalian development, transit rapidly through early development 4 3 (E3.5-E5.5, i.e. ~2 days), followed by development of the characteristic cup-shaped post- inaccessible, we are beginning to investigate relatively more accessible pig embryos. 8Notably both human and pig embryos evidently form a flat embryonic disc before the onset 4 9 of gastrulation 4 . Thus, the pig embryo can broaden our understanding of the pre-gastrulation 5 0development of large mammals with protracted development. 1Segregation of trophectoderm (TE) and hypoblast, and the emergence of pluripotency arewell established in mice 5,6 , but require detailed studies in other mammals at the resolution of lineage segregation have however emerged in reports between monkey and human, large mammalian species, are therefore highly desirable. 7In mouse embryos a distinct transcriptional signature of naïve pluripotency in the inner cell humans, has been challenging, suggesting possible biological differences 9,10 . Indeed, mouse embryonic naïve cells are not apparently detected in human embryos 9,11 . By contrast, . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/347823 doi: bioRxiv preprint first posted online Jun. 20, 2018; 4 KLF17 is expressed in the human but not mouse ICM 9,11,12 . Also, while Jak-Stat3 and WNT 6 7 signalling are detected in the early mouse ICM 13 , many TGFβ signalling components are 6 8 present in marmoset, human and pig ICM 11,12,14,15 , indicating that the emergence and been studied 12,16 . 5Here we report lineage segregation, the establishment of pluripotency, and X-chromosomeinactivation during the entire peri-gastrulation period in the pig embryo using single cell RNA-seq (scRNA-seq). This comprehensive analysis provides new understanding of the the early human developmen...

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Section: Resultssupporting

confidence: 89%

Lineage segregation, pluripotency and X-chromosome inactivation in the pig pre-gastrulation embryo

Ramos‐Ibeas

Sang²,

Zhu

et al. 2018

Preprint

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“…The TE markers reported in mice and humans such as KRT8, DAB2, CDX2 and TEAD4 were also highly expressed in porcine TE. Notably, as we previously reported, 19,24 OCT4 expressed widely in ICM and TE. Expression of some pluripotent genes such as SOX2, KLF4 and OTX2 was observed in ICM.…”

Section: Segregation Of Icm and Te In Porcine Ebsupporting

confidence: 70%

Lineage specification and pluripotency revealed by transcriptome analysis from oocyte to blastocyst in pig

Kong

Zhang

et al. 2019

The FASEB Journal

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The inner cell mass (ICM) in blastocyst is the origin of all somatic and germ cells in mammals and pluripotent stem cells (PSCs) in vitro. As the conserved principles between pig and human, here we performed comprehensive single‐cell RNA‐seq for porcine early embryos from oocyte to early blastocyst (EB). We show the specification of the ICM and trophectoderm in morula and the molecular signature of the precursors. We demonstrate the existence of naïve pluripotency signature in morula and ICM of EB, and the specific pluripotent genes and the activity of signalling pathways highlight the characteristics of the naïve pluripotency. We observe the absence of dosage compensation with respect to X‐chromosome (XC) in morula, and incomplete dosage compensation in the EB. However, the dynamics of dosage compensation may be independent of the expression of XIST induced XC inactivation. Our study describes molecular landmarks of embryogenesis in pig that will provide a better strategy for derivation of porcine PSCs and improve research in regenerative medicine.

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“…However, our results showed a quite different expression pattern of the Cdx2 protein between the pig and the mouse during blastocyst formation (Bou et al, ; Liu et al, ). In mice, CDX2 initiates expression as early as the eight‐cell stage in one or two blastomeres.…”

Section: Introductionmentioning

confidence: 65%

“…Either up‐ or downregulation of Cdx2 in single blastomeres at the two‐ or four‐cell stage leads to an increased or decreased contribution to TE, respectively. Recently, our lab has also shown a key role of Cdx2 in porcine TE cells (Bou et al, ). Cdx2 is necessary for porcine trophoblast cell proliferation and the maintenance of cell polarity.…”

Section: Introductionmentioning

confidence: 94%

Asynchronous CDX2 expression and polarization of porcine trophoblast cells reflects a species‐specific trophoderm lineage determination progress model

Liu

Bou

Zhao

et al. 2018

Molecular Reproduction Devel

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Upregulation of Cdx2 expression in outer cells is a key event responsible for cell lineage segregation between the inner cell mass and the trophoderm (TE) in mouse morula-stage embryos. In TE cells, polarization can regulate Hippo and Rho-associated kinase (Rho-ROCK) signaling to induce the nuclear location of YAP, which has been demonstrated to further induce the expression of Cdx2. However, we found that CDX2 expression could not be detected in the outer cells of porcine morula-stage embryos but only in some TE cells at the early blastocyst stage. The biological significance and the regulation mechanism of this species-specific CDX2 expression pattern have still not been determined. We show here that an asynchronous CDX2 expression pattern exists in porcine TE cells during the development of the blastocyst. We demonstrate that CDX2 expression in porcine TE cells depends on the nuclear localization of YAP and polarization of the embryo through Y27632 treatment. We found that the polarization process in the morula to the late blastocyst stage porcine embryos was asynchronous, which was revealed by the apical localization of phosphorylated EZRIN staining. Artificially enhancing the number of polarized blastomeres by culturing the separated blastomeres of four-cell stage porcine embryos resulted in increased CDX2-positive cell numbers. These results indicate that the mechanism of CDX2 expression regulation is conserved, but the polarization progress is not conserved between the pig and the mouse, and results in a species-specific trophoblast determination progress model.

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CDX2 is essential for cell proliferation and polarity in porcine blastocysts

Cited by 67 publications

References 56 publications

Lineage segregation, pluripotency and X-chromosome inactivation in the pig pre-gastrulation embryo

Lineage segregation, pluripotency and X-chromosome inactivation in the pig pre-gastrulation embryo

Lineage specification and pluripotency revealed by transcriptome analysis from oocyte to blastocyst in pig

Asynchronous CDX2 expression and polarization of porcine trophoblast cells reflects a species‐specific trophoderm lineage determination progress model

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