Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Generation of somatic chimeras using genetically-reprogrammed rabbits induced pluripotent stem cells [KEPc]

ABSTRACT: Little is known about the molecular underpinnings of pluripotent stem cells (PSCs)’ ability to colonize preimplantation embryo epiblast to generate chimeras. Using rabbit PSCs as a model system, we conducted unbiased screening of a cDNA library encoding a panel of 36 pluripotency factors. From this, we identified KLF2, ERAS and PRMT6 whose overexpression endows the ability to self-renew in a KOSR/FGF2-free culture medium supplemented with LIF, activin A, PKC and WNT inhibitors. The reprogrammed cells acquired transcriptomic and epigenetic features of naïve pluripotency, including the reactivation of the 2nd X-chromosome. Leveraging on these PSC lines, we determined the transcriptomic signature of embryonic colonization-competence, demonstrating transcriptional repression of genes involved in MAPK, WNT, HIPPO, and EPH signaling pathways, and activation of genes involved in amino-acid metabolism, NF-kB signaling, and p53 pathway. Remarkably, these reprogrammed cells acquired the ability to produce chimeric embryos and fetuses with high contribution from PSCs in all major organs.

ORGANISM(S): Oryctolagus cuniculus

PROVIDER: GSE250261 | GEO | 2024/12/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Generation of somatic chimeras using genetically-reprogrammed rabbits induced pluripotent stem cells [KEPi]

Project description:Little is known about the molecular underpinnings of pluripotent stem cells (PSCs)’ ability to colonize preimplantation embryo epiblast to generate chimeras. Using rabbit PSCs as a model system, we conducted unbiased screening of a cDNA library encoding a panel of 36 pluripotency factors. From this, we identified KLF2, ERAS and PRMT6 whose overexpression endows the ability to self-renew in a KOSR/FGF2-free culture medium supplemented with LIF, activin A, PKC and WNT inhibitors. The reprogrammed cells acquired transcriptomic and epigenetic features of naïve pluripotency, including the reactivation of the 2nd X-chromosome. Leveraging on these PSC lines, we determined the transcriptomic signature of embryonic colonization-competence, demonstrating transcriptional repression of genes involved in MAPK, WNT, HIPPO, and EPH signaling pathways, and activation of genes involved in amino-acid metabolism, NF-kB signaling, and p53 pathway. Remarkably, these reprogrammed cells acquired the ability to produce chimeric embryos and fetuses with high contribution from PSCs in all major organs.

2024-12-03 | GSE250287 | GEO

Molecular and functional features demarcate embryonic and induced pluripotent stem cells in rabbits

Project description:Little is known about the molecular and functional features of pluripotent stem cells (PSCs) in rabbits. To address this, we derived and characterized two types of rabbit PSCs from the same breed of New Zealand White rabbits: four lines of embryonic stem cells (rbESCs), and three lines of induced PSCs (rbiPSCs) that resulted from reprogramming adult skin fibroblasts. All lines were dependent on fibroblast growth factor 2. All rbESC lines exhibited molecular and functional properties typically associated with primed pluripotency. The rbESC lines also exhibited a cell cycle with a prolonged G1 phase and a DNA damage checkpoint prior to entry into the S phase, which are two features typically associated with the somatic cell cycle. In contrast, the rbiPSC lines exhibited some characteristics of naÃ¯ve pluripotency as defined in rodents, including resistance to single cell dissociation by trypsin, robust activity of the distal enhancer of the mouse Oct4 gene, and expression of naÃ¯ve-specific genes. According to gene expression profiles, rbiPSCs were closer to the rabbit inner cell mass than rbESCs. We propose that rbiPSCs self-renew in an intermediate state between naÃ¯ve and primed pluripotency, which represents a key step toward the generation of bona fide naÃ¯ve PSC lines in rabbits The patterns of stage specific embryonic antigen (SSEA) expression were also assessed between cell lines. All two rbiPSC lines exhibited heterogeneous expression of SSEA1 and SSEA4 that leads to obtain 3 different cell sub-populations (SSEA1+, SSEA1+/4+, SSEA1-/4-). All four rbESC lines expressed only SSEA1 and not SSEA4. Then, for this category of cell lines, we used 3 different cell sub-populations (SSEA1+, SSEA1-, and total which contained all cell types). Three independent experiments were performed for each line and for each cell sub-population.

2013-01-11 | E-GEOD-43403 | biostudies-arrayexpress

Molecular and functional features demarcate embryonic and induced pluripotent stem cells in rabbits

Project description:Little is known about the molecular and functional features of pluripotent stem cells (PSCs) in rabbits. To address this, we derived and characterized two types of rabbit PSCs from the same breed of New Zealand White rabbits: four lines of embryonic stem cells (rbESCs), and three lines of induced PSCs (rbiPSCs) that resulted from reprogramming adult skin fibroblasts. All lines were dependent on fibroblast growth factor 2. All rbESC lines exhibited molecular and functional properties typically associated with primed pluripotency. The rbESC lines also exhibited a cell cycle with a prolonged G1 phase and a DNA damage checkpoint prior to entry into the S phase, which are two features typically associated with the somatic cell cycle. In contrast, the rbiPSC lines exhibited some characteristics of naïve pluripotency as defined in rodents, including resistance to single cell dissociation by trypsin, robust activity of the distal enhancer of the mouse Oct4 gene, and expression of naïve-specific genes. According to gene expression profiles, rbiPSCs were closer to the rabbit inner cell mass than rbESCs. We propose that rbiPSCs self-renew in an intermediate state between naïve and primed pluripotency, which represents a key step toward the generation of bona fide naïve PSC lines in rabbits

2013-01-11 | GSE43403 | GEO

Generation of somatic chimeras using genetically-reprogrammed rabbits induced pluripotent stem cells

Project description:Generation of somatic chimeras using genetically-reprogrammed rabbits induced pluripotent stem cells

| PRJNA1053304 | ENA

Global Profiling of the Lysine Crotonylome in Different Pluripotent States

Project description:Understanding the mechanisms of pluripotency maintenance and exit are important for developmental biology and regenerative medicine. However, studies of pluripotency and post-translational modifications of proteins are scarce. To systematically profile protein crotonylation in mouse pluripotent stem cells (PSCs) in different culture conditions, we used affinity purification of crotonylated peptides, TMT labeling, and LC-MS/MS. Our study included PSCs in ground, metastable, and primed state, as well as metastable PSCs undergoing early pluripotency exit. We have successfully identified 8,102 crotonylation sites in 2,578 proteins, among which 3,628 sites in 1,426 proteins were with high-confidence. These high-confidence crotonylated proteins are enriched for factors involved in functions related to pluripotency such as RNA biogenesis, central carbon metabolism, and proteasome function. Our atlas of protein crotonylation will be valuable for further studies of pluripotency regulation and may also provide insights into the role of crotonylation in other cell fate transitions.

2021-02-26 | PXD017121 | Pride

Principles of Signalling Pathway Modulation for Enhancing Human Naïve Pluripotency Induction [ChIP-seq]

Project description:Isolating human MEK/ERK signalling independent pluripotent stem cells (PSCs) with characteristics of naive pluripotency while maintaining differentiation competence and genetic integrity, remains challenging. Here we engineer reporter systems that allow screening for conditions that induce molecular and functional features of human naive pluripotency. Synergistic inhibition of WNT-ßCATENIN, PKC and SRC signalling enables induction of teratoma competent naïve human PSCs, with capacity to differentiate into trophoblast stem cells (TSC) and extraembryonic endodermal (XEN) cells in vitro. Divergent signalling and transcriptional requirements for boosting naïve pluripotency were found between mouse and human. P53 depletion in human naïve PSCs endows them with competitiveness to better contribute to mouse-human cross-species chimeric embryos upon priming. Finally, MEK/ERK inhibition can be substituted with inhibition for NOTCH/RBPj, which allows inducing alternative human naïve-like PSCs with diminished risk for deleterious global DNA hypomethylation. Our findings set a framework for defining the signalling foundations of human naïve pluripotency.

2021-03-25 | GSE125553 | GEO

Principles of Signalling Pathway Modulation for Enhancing Human Naïve Pluripotency Induction [ATAC-Seq]

2021-03-25 | GSE124614 | GEO