Generation of genome-edited mouse epiblast stem cells via a detour through ES cell-chimeras

AbstractThe pluripotency of mammalian early and late epiblast could be recapitulated by naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), respectively. However, these two states of pluripotency may not be sufficient to reflect the full complexity and developmental potency of the epiblast during mammalian early development. Here we report the establishment of self-renewing formative pluripotent stem cells (fPSCs) which manifest features of epiblast cells poised for gastrulation. fPSCs can be established from different mouse ESCs, pre-/early-gastrula epiblasts and induced PSCs. Similar to pre-/early-gastrula epiblasts, fPSCs show the transcriptomic features of formative pluripotency, which are distinct from naïve ESCs and primed EpiSCs. fPSCs show the unique epigenetic states of E6.5 epiblast, including the super-bivalency of a large set of developmental genes. Just like epiblast cells immediately before gastrulation, fPSCs can efficiently differentiate into three germ layers and primordial germ cells (PGCs) in vitro. Thus, fPSCs highlight the feasibility of using PSCs to explore the development of mammalian epiblast.

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High‐throughput screening in postimplantation haploid epiblast stem cells reveals Hs3st3b1 as a modulator for reprogramming

Stem Cells Translational Medicine ◽

10.1002/sctm.20-0468 ◽

2021 ◽

Author(s):

Qian Gao ◽

Wenhao Zhang ◽

Yiding Zhao ◽

Yaru Tian ◽

Yuna Wang ◽

...

Keyword(s):

Stem Cells ◽

High Throughput ◽

High Throughput Screening ◽

Epiblast Stem Cells

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Germ line transmission of an inactive N-myc allele generated by homologous recombination in mouse embryonic stem cells

Molecular and Cellular Biology ◽

10.1128/mcb.10.12.6755-6758.1990 ◽

1990 ◽

Vol 10 (12) ◽

pp. 6755-6758

Author(s):

B R Stanton ◽

S W Reid ◽

L F Parada

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Homologous Recombination ◽

Embryonic Development ◽

Cell Lines ◽

Germ Line ◽

Es Cells ◽

Embryonic Stem ◽

Es Cell ◽

Germ Line Transmission

We have disrupted one allele of the N-myc locus in mouse embryonic stem (ES) cells by using homologous recombination techniques and have obtained germ line transmission of null N-myc ES cell lines with transmission of the null N-myc allele to the offspring. The creation of mice with a deficient N-myc allele will allow the generation of offspring bearing null N-myc alleles in both chromosomes and permit study of the role that this proto-oncogene plays in embryonic development.

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Human embryonic stem cells: challenges and opportunities

Reproduction Fertility and Development ◽

10.1071/rd06113 ◽

2006 ◽

Vol 18 (8) ◽

pp. 839 ◽

Cited By ~ 3

Author(s):

Steven L. Stice ◽

Nolan L. Boyd ◽

Sujoy K. Dhara ◽

Brian A. Gerwe ◽

David W. Machacek ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Cell Line ◽

Cell Fate ◽

Neural Development ◽

Es Cells ◽

Embryonic Stem ◽

Normal Karyotype ◽

Es Cell ◽

Cell Therapies

Human and non-human primate embryonic stem (ES) cells are invaluable resources for developmental studies, pharmaceutical research and a better understanding of human disease and replacement therapies. In 1998, subsequent to the establishment of the first monkey ES cell line in 1995, the first human ES cell line was developed. Later, three of the National Institute of Health (NIH) lines (BG01, BG02 and BG03) were derived from embryos that would have been discarded because of their poor quality. A major challenge to research in this area is maintaining the unique characteristics and a normal karyotype in the NIH-registered human ES cell lines. A normal karyotype can be maintained under certain culture conditions. In addition, a major goal in stem cell research is to direct ES cells towards a limited cell fate, with research progressing towards the derivation of a variety of cell types. We and others have built on findings in vertebrate (frog, chicken and mouse) neural development and from mouse ES cell research to derive neural stem cells from human ES cells. We have directed these derived human neural stem cells to differentiate into motoneurons using a combination of developmental cues (growth factors) that are spatially and temporally defined. These and other human ES cell derivatives will be used to screen new compounds and develop innovative cell therapies for degenerative diseases.

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Designer blood: creating hematopoietic lineages from embryonic stem cells

Blood ◽

10.1182/blood-2005-09-3621 ◽

2006 ◽

Vol 107 (4) ◽

pp. 1265-1275 ◽

Cited By ~ 51

Author(s):

Abby L. Olsen ◽

David L. Stachura ◽

Mitchell J. Weiss

Keyword(s):

Stem Cells ◽

Es Cells ◽

Embryonic Stem ◽

Basic Research ◽

Cell Types ◽

Patient Specific ◽

Es Cell ◽

Blood Disorders ◽

Hematopoietic Stem

Embryonic stem (ES) cells exhibit the remarkable capacity to become virtually any differentiated tissue upon appropriate manipulation in culture, a property that has been beneficial for studies of hematopoiesis. Until recently, the majority of this work used murine ES cells for basic research to elucidate fundamental properties of blood-cell development and establish methods to derive specific mature lineages. Now, the advent of human ES cells sets the stage for more applied pursuits to generate transplantable cells for treating blood disorders. Current efforts are directed toward adapting in vitro hematopoietic differentiation methods developed for murine ES cells to human lines, identifying the key interspecies differences in biologic properties of ES cells, and generating ES cell-derived hematopoietic stem cells that are competent to repopulate adult hosts. The ultimate medical goal is to create patient-specific and generic ES cell lines that can be expanded in vitro, genetically altered, and differentiated into cell types that can be used to treat hematopoietic diseases.

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