Dppa2/4 as a trigger of signaling pathways to promote zygote genome activation by binding to CG-rich region

2020 ◽  
Author(s):  
Hanshuang Li ◽  
Chunshen Long ◽  
Jinzhu Xiang ◽  
Pengfei Liang ◽  
Xueling Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
Embryonic Stem ◽  
Proximal Promoter ◽  
Human Embryos ◽  
Double Knockout ◽  
Rich Region ◽  
Induced Pluripotent ◽  
Zygote Genome Activation ◽  
Genome Activation

Abstract Developmental pluripotency-associated 2 (Dppa2) and developmental pluripotency-associated 4 (Dppa4) as positive drivers were helpful for transcriptional regulation of zygotic genome activation (ZGA). Here, we systematically assessed the cooperative interplay of Dppa2 and Dppa4 in regulating cell pluripotency and found that simultaneous overexpression of Dppa2/4 can make induced pluripotent stem cells closer to embryonic stem cells (ESCs). Compared with other pluripotency transcription factors, Dppa2/4 can regulate majorities of signaling pathways by binding on CG-rich region of proximal promoter (0–500 bp), of which 85% and 77% signaling pathways were significantly activated by Dppa2 and Dppa4, respectively. Notably, Dppa2/4 also can dramatically trigger the decisive signaling pathways for facilitating ZGA, including Hippo, MAPK and TGF-beta signaling pathways and so on. At last, we found alkaline phosphatase, placental-like 2 (Alppl2) was completely silenced when Dppa2 and 4 single- or double-knockout in ESC, which is consistent with Dux. Moreover, Alppl2 was significantly activated in mouse 2-cell embryos and 4–8 cells stage of human embryos, further predicted that Alppl2 was directly regulated by Dppa2/4 as a ZGA candidate driver to facilitate pre-embryonic development.

scholarly journals Dppa2/4 promotes zygotic genome activation by binding to GC-rich region in signaling pathways

2020 ◽  
Author(s):  
Hanshuang Li ◽  
Chunshen Long ◽  
Jinzhu Xiang ◽  
Pengfei Liang ◽  
Yongchun Zuo
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
Embryonic Stem ◽  
Cell Types ◽  
Proximal Promoter ◽  
Human Embryos ◽  
Rich Region ◽  
Cell Stage ◽  
Potent Effect ◽  
Induced Pluripotent

AbstractDevelopmental pluripotency associated 2 (Dppa2) and Dppa4 as positive drivers were helpful for transcriptional regulation of ZGA. Here, we systematically assessed the cooperative interplay between Dppa2 and Dppa4 in regulating cell pluripotency of three cell types and found that simultaneous overexpression of Dppa2/4 can make induced pluripotent stem cells closer to embryonic stem cells. Compared with other pluripotency transcription factors (TFs), Dppa2/4 tends to bind on GC-rich region of proximal promoter (0-500bp). Moreover, there was more potent effect of Dppa2/4 regulation on signaling pathways than other TFs, in which 75% and 85% signaling pathways were significantly activated by Dppa2 and Dppa4, respectively. Notably, Dppa2/4 also can dramatically trigger the decisive signaling pathways for facilitating ZGA, including Hippo, MAPK and TGF-beta signaling pathways and so on. At last, we found that Alkaline phosphatase placental-like 2 (Alppl2) was significantly activated at the 2-cell stage in mouse embryos and 4-8 cell stage in human embryos, further predicted that Alppl2 was directly regulated by Dppa2/4 as a candidate driver of ZGA to regulate pre-embryonic development.

scholarly journals Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Elo Madissoon ◽  
Eeva-Mari Jouhilahti ◽  
Liselotte Vesterlund ◽  
Virpi Töhönen ◽  
Kaarel Krjutškov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Target Genes ◽  
Genomic Sequence ◽  
Embryonic Stem ◽  
Homeobox Genes ◽  
Preimplantation Embryos ◽  
Human Embryos ◽  
Preimplantation Embryo Development ◽  
Genome Activation

Abstract PAIRED (PRD)-like homeobox genes belong to a class of predicted transcription factor genes. Several of these PRD-like homeobox genes have been predicted in silico from genomic sequence but until recently had no evidence of transcript expression. We found recently that nine PRD-like homeobox genes, ARGFX, CPHX1, CPHX2, DPRX, DUXA, DUXB, NOBOX, TPRX1 and TPRX2, were expressed in human preimplantation embryos. In the current study we characterized these PRD-like homeobox genes in depth and studied their functions as transcription factors. We cloned multiple transcript variants from human embryos and showed that the expression of these genes is specific to embryos and pluripotent stem cells. Overexpression of the genes in human embryonic stem cells confirmed their roles as transcription factors as either activators (CPHX1, CPHX2, ARGFX) or repressors (DPRX, DUXA, TPRX2) with distinct targets that could be explained by the amino acid sequence in homeodomain. Some PRD-like homeodomain transcription factors had high concordance of target genes and showed enrichment for both developmentally important gene sets and a 36 bp DNA recognition motif implicated in Embryo Genome Activation (EGA). Our data implicate a role for these previously uncharacterized PRD-like homeodomain proteins in the regulation of human embryo genome activation and preimplantation embryo development.

Actual strategies in human induced pluripotent stem cells (hiPSCs) differentiation – perspectives and challenges

2016 ◽  
Vol 52 (2) ◽  
pp. 123-136
Author(s):  
Ewelina Augustyniak ◽  
Katarzyna Kulcenty ◽  
Michał Lach ◽  
Igor Piotrowski ◽  
Wiktoria Maria Suchorska
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Patient Specific ◽  
Human Embryos ◽  
Alternative Approaches ◽  
Induced Pluripotent ◽  
Autologous Grafts ◽  
Derivatives Of

The application of stem cells (SCs) in regenerative medicine has recently become a rapidly growing field, holding promise for combating a number of currently incurable disorders: including diabetes, neurodegenerative, retinal and cardiac diseases, as well as muscular dystrophy. The search for alternative approaches led to the development of human induced pluripotent stem cells (hiPSCs) which have unrestricted proliferative activity and pluripotency – the capacity to differentiation into derivatives of three germ layers (meso-, ecto – and endoderm). Because hiPSCs are developed from adult human cells throughout the forced expression of pluripotency factors, they are free from the ethical concerns associated with human embryonic stem cells (hESCs), that creation involves the destruction of human embryos. Moreover, the use of hiPSCs contributes to the development of personalized medicine that exploits patient-specific cells extremely useful in autologous grafts. In the present study the methods of hiPSCs differentiation into stem cell-derived neurons, cardiomyocytes, chondrocytes and osteocytes were summarized and evaluated having regard to their most important aspects.

scholarly journals Single-cell RNA sequencing reveals that BMPR2 mutation regulates right ventricular function via ID genes

2021 ◽  
pp. 2100327
Author(s):  
Mingxia Du ◽  
Haibin Jiang ◽  
Hongxian Liu ◽  
Xin Zhao ◽  
Yu Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Single Cell ◽  
Heart Development ◽  
Pulmonary Regurgitation ◽  
Embryonic Stem ◽  
Cardiac Differentiation ◽  
Double Knockout ◽  
Morphogenetic Protein ◽  
Downstream Effectors ◽  
Induced Pluripotent

Mutations in bone morphogenetic protein type II receptor (BMPR2) have been found in patients with congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH). Our study aimed to clarify whether deficient BMPR2 signalling acts through downstream effectors, inhibitors of DNA-binding proteins (IDs), during heart development to contribute to the progress of PAH in CHD patients. To confirm that IDs are downstream effectors of BMPR2 signalling in cardiac mesoderm progenitors (CMPs) and contribute to PAH, we generated Cardiomyocytes (CMs)-specific Id 1/3 knockout mice (Ids cDKO), and 12/25 developed mild PAH with altered haemodynamic indices and pulmonary vascular remodelling. Moreover, we generated ID1 and ID3 double-knockout (IDs KO) human embryonic stem cells that recapitulated the BMPR2 signalling deficiency of CHD-PAH iPSCs. CMs differentiated from induced pluripotent stem cells (iPSCs) derived from CHD-PAH patients with BMPR mutations exhibited dysfunctional cardiac differentiation and reduced Ca2+ transients, as evidenced by confocal microscopy experiments. Smad1/5 phosphorylation and ID1 and ID3 expression were reduced in CHD-PAH iPSCs and in Bmpr2+/– rat right ventricles. Moreover, Ultrasound revealed that 33% of Ids cDKO mice had detectable defects in their ventricular septum and pulmonary regurgitation. CMs isolated from the mouse right ventricles also showed reduced Ca2+ transients and shortened sarcomeres. Single-cell RNA(scRNA)-seq analysis revealed impaired differentiation of CMPs and downregulated USP9X expression in IDs KO cells compared with wild-type (WT) cells. We found that BMPR2 signals through IDs and USP9X to regulate cardiac differentiation, and the loss of ID1 and ID3 expression contributes to CM dysfunction in CHD-PAH patients with BMPR2 mutations.

Mini Review; Differentiation of Human Pluripotent Stem Cells into Oocytes

2020 ◽  
Vol 15 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Gaifang Wang ◽  
Maryam Farzaneh
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Human Pluripotent Stem Cells ◽  
Human Oocyte ◽  
Differentiation Potential ◽  
Cell Lineages ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility that occurs in about 1% of women between 30-40 years of age. There are few effective methods for the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation into oocytes have not been fully investigated. Therefore, in this review, we focus on the differentiation potential of hPSCs into human oocyte-like cells.

A New Feeder-Free Technique to Expand Human Embryonic Stem Cells and Induced Pluripotent Stem Cells

2009 ◽  
Vol 1 (1) ◽  
pp. 76-82 ◽  
Author(s):  
Mark Denham ◽  
Jessie Leung ◽  
Cheryl Tay ◽  
Raymond C.B. Wong ◽  
Peter Donovan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Induced Pluripotent

scholarly journals Embryoid research calls for reassessment of legal regulations

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Markus Hengstschläger ◽  
Margit Rosner
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Legal Status ◽  
Embryonic Stem ◽  
Basic Research ◽  
Human Embryos ◽  
Human Being ◽  
Legal Regulations ◽  
Definition Of

AbstractIt is known that in countries, in which basic research on human embryos is in fact prohibited by law, working with imported human embryonic stem cells (hESCs) can still be permitted. As long as hESCs are not capable of development into a complete human being, it might be the case that they do not fulfill all criteria of the local definition of an embryo. Recent research demonstrates that hESCs can be developed into entities, called embryoids, which increasingly could come closer to actual human embryos in future. By discussing the Austrian situation, we want to highlight that current embryoid research could affect the prevailing opinion on the legal status of work with hESCs and therefore calls for reassessment of the regulations in all countries with comparable definitions of the embryo.

scholarly journals Strategy to Establish Embryo-Derived Pluripotent Stem Cells in Cattle

2021 ◽  
Vol 22 (9) ◽  
pp. 5011
Author(s):  
Daehwan Kim ◽  
Sangho Roh
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Stem Cell Research ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Culture Conditions ◽  
Human Diseases ◽  
Induced Pluripotent

Stem cell research is essential not only for the research and treatment of human diseases, but also for the genetic preservation and improvement of animals. Since embryonic stem cells (ESCs) were established in mice, substantial efforts have been made to establish true ESCs in many species. Although various culture conditions were used to establish ESCs in cattle, the capturing of true bovine ESCs (bESCs) has not been achieved. In this review, the difficulty of establishing bESCs with various culture conditions is described, and the characteristics of proprietary induced pluripotent stem cells and extended pluripotent stem cells are introduced. We conclude with a suggestion of a strategy for establishing true bESCs.

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