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Your search keyword '"Zou, Xiangang"' showing total 3 results
Start Over Author "Zou, Xiangang" Topic induced pluripotent stem cells
3 results on '"Zou, Xiangang"'

1. Establishment of porcine and human expanded potential stem cells.

Author

Gao X, Nowak-Imialek M, Chen X, Chen D, Herrmann D, Ruan D, Chen ACH, Eckersley-Maslin MA, Ahmad S, Lee YL, Kobayashi T, Ryan D, Zhong J, Zhu J, Wu J, Lan G, Petkov S, Yang J, Antunes L, Campos LS, Fu B, Wang S, Yong Y, Wang X, Xue SG, Ge L, Liu Z, Huang Y, Nie T, Li P, Wu D, Pei D, Zhang Y, Lu L, Yang F, Kimber SJ, Reik W, Zou X, Shang Z, Lai L, Surani A, Tam PPL, Ahmed A, Yeung WSB, Teichmann SA, Niemann H, and Liu P

Subjects
Animals, Blastomeres cytology, Blastomeres metabolism, Cell Lineage genetics, Embryonic Stem Cells cytology, Germ Layers growth & development, Germ Layers metabolism, Humans, Mice, Regenerative Medicine, Signal Transduction genetics, Swine, Trophoblasts cytology, Trophoblasts metabolism, Cell Differentiation genetics, Cellular Reprogramming genetics, Induced Pluripotent Stem Cells cytology, Pluripotent Stem Cells cytology
Abstract

We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine.

Published
2019
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2. In vitro establishment of expanded-potential stem cells from mouse pre-implantation embryos or embryonic stem cells.

Author

Yang J, Ryan DJ, Lan G, Zou X, and Liu P

Subjects
Animals, Biomarkers metabolism, Blastomeres cytology, Blastomeres metabolism, CDX2 Transcription Factor genetics, CDX2 Transcription Factor metabolism, Cell Differentiation, Cell Proliferation, Cellular Reprogramming, Endoderm cytology, Endoderm metabolism, Female, Fibroblasts cytology, Fibroblasts metabolism, Gene Expression, Germ Layers cytology, Germ Layers metabolism, Induced Pluripotent Stem Cells metabolism, Mice, Mice, Inbred C57BL, Mouse Embryonic Stem Cells metabolism, Octamer Transcription Factor-3 genetics, Octamer Transcription Factor-3 metabolism, Primary Cell Culture, Trophoblasts metabolism, Cell Culture Techniques, Cell Lineage, Embryonic Development, Induced Pluripotent Stem Cells cytology, Mouse Embryonic Stem Cells cytology, Trophoblasts cytology
Abstract

Molecular and embryology studies have demonstrated that mouse pre-implantation embryo development is a process of progressive cell fate determination. At the time of implantation, three cell lineages are present in the developing blastocyst: the trophectoderm (TE), the epiblast (Epi) and the primitive endoderm (PrE). From these early embryo cells, trophoblast stem (TS) cells, embryonic stem (ES) cells and extra-embryonic endoderm stem (XEN) cells can be derived. Recently, we derived stem cells with blastomere-like features from mouse cleavage-stage embryos, which we named expanded-potential stem cells (EPSCs). Here, we provide detailed protocols that describe how to establish EPSCs from single eight-cell-stage blastomeres or whole eight-cell pre-implantation mouse embryos, or by conversion of mouse ES cells or induced pluripotent stem (iPS) cells reprogrammed from fibroblasts. It takes 2-3 weeks to derive EPSCs from each cell source. The EPSCs derived from these protocols can differentiate into all embryonic and extra-embryonic lineages when implanted into chimeras. Furthermore, bona fide TS and XEN cell lines can be derived from EPSCs in vitro.

Published
2019
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3. Genome-Scale CRISPRa Screen Identifies Novel Factors for Cellular Reprogramming

Author

Yang, Jian, Rajan, Sandeep S, Friedrich, Mathias J, Lan, Guocheng, Zou, Xiangang, Ponstingl, Hannes, Garyfallos, Dimitrios A, Liu, Pentao, Bradley, Allan, Metzakopian, Emmanouil, Bradley, Allan [0000-0002-2349-8839], and Apollo - University of Cambridge Repository

Subjects
Pluripotent Stem Cells, epiblast stem cells, induced pluripotent stem cells, genome-wide screen, Gene Dosage, Article, CRISPR screen, Cell Line, Mice, Animals, Humans, Clustered Regularly Interspaced Short Palindromic Repeats, lcsh:QH301-705.5, CRISPR/Cas9, reprogramming pathways, lcsh:R5-920, gain-of-function, CRISPR activation, activation screen, reprogramming, Cellular Reprogramming, lcsh:Biology (General), embryonic structures, CRISPR-Cas Systems, lcsh:Medicine (General), Octamer Transcription Factor-3, Biomarkers, Germ Layers, Genome-Wide Association Study, Transcription Factors
Abstract

Summary Primed epiblast stem cells (EpiSCs) can be reverted to a pluripotent embryonic stem cell (ESC)-like state by expression of single reprogramming factor. We used CRISPR activation to perform a genome-scale, reprogramming screen in EpiSCs and identified 142 candidate genes. Our screen validated a total of 50 genes, previously not known to contribute to reprogramming, of which we chose Sall1 for further investigation. We show that Sall1 augments reprogramming of mouse EpiSCs and embryonic fibroblasts and that these induced pluripotent stem cells are indeed fully pluripotent including formation of chimeric mice. We also demonstrate that Sall1 synergizes with Nanog in reprogramming and that overexpression in ESCs delays their conversion back to EpiSCs. Lastly, using RNA sequencing, we identify and validate Klf5 and Fam189a2 as new downstream targets of Sall1 and Nanog. In summary, our work demonstrates the power of using CRISPR technology in understanding molecular mechanisms that mediate complex cellular processes such as reprogramming., Graphical Abstract, Highlights • Genome-scale CRISPRa screen in mouse EpiSCs identifies novel reprogramming factors • 50 novel genes, including Sall1 and Fam189a2, identified to mediate reprogramming • Sall1 synergizes with Nanog to increase reprogramming efficiency in EpiSCs and MEFs • RNA-seq provides insight into downstream pathways of Sall1 and Nanog-mediated reprogramming, In this study, Metzakopian and colleagues use CRISPR activation to perform a genome-scale reprogramming screen on mouse epiblast stem cells identifying 50 novel candidates. In addition, the authors provide evidence of Sall1 being a potent reprogramming gene, capable of synergizing with Nanog. Lastly, using RNA-seq, the authors provide insight into potential downstream targets of Sall1 and Nanog.

Published
2019

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