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Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Rattus norvegicus

PROVIDER: GSE167435 | GEO | 2022/08/01

REPOSITORIES: GEO

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Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells [scRNAseq_chimera]

Project description:Pluripotent stem cells (PSCs) provide a powerful tool to produce transgenic animals for biomedical research. However, impaired PSC contribution to chimerism and most notably the germline oftentimes impedes production of genetically modified animals, rendering techniques that expediate PSC contribution to the germline highly desirable. Blastocyst complementation denotes a technique which purposes to generate organs, tissues or cells in animal chimeras via microinjection of PSCs into genetically compromised blastocyst-stage embryos. Here we report on successful blastocyst complementation of the male germline in adult chimeras following microinjection of mouse or rat PSCs into mouse blastocysts mutated for Tsc22d3, an essential gene for spermatozoa production. Microinjection of mouse embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) into Tsc22d3-KnockOut (KO) blastocyst-stage embryos gave rise to intraspecies chimeras embodying functional spermatozoa, which were solely derived from microinjected PSCs. Furthermore, microinjection of rat ESCs into Tsc22d3-KO mouse embryos gave rise to viable mouse-rat chimeras that exhibited extensive contribution of rat cells to various organs. Notably, multiple mouse-rat chimeras showed contribution of rat ESCs to the male germline, solely harboring rat spermatids and spermatozoa that were rat ESC-derived and could fertilize rat oocytes. Collectively, this study reports a method for exclusive production of functional germ cells of one species in another via blastocyst complementation with PSCs. Implications of this study extend to development of transgenic rats via sterile mice, and may further assist efforts to generate xenogeneic gametes from endangered animal species.

2022-08-01 | GSE202699 | GEO

Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells [scRNAseq_rat]

Project description:Pluripotent stem cells (PSCs) provide a powerful tool to produce transgenic animals for biomedical research. However, impaired PSC contribution to chimerism and most notably to the germline oftentimes impedes production of genetically modified animals, rendering techniques that expediate PSC contribution to the germline highly desirable. Blastocyst complementation denotes a technique which purposes to generate organs, tissues or cells in animal chimeras following microinjection of PSCs into genetically compromised blastocyst-stage embryos. Here, we report on successful blastocyst complementation of the male germline in adult chimeras via microinjection of mouse or rat PSCs into mouse blastocysts mutated for Tsc22d3, an essential gene for spermatozoa production. Microinjection of mouse embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) into Tsc22d3-KnockOut (KO) blastocyst-stage embryos gave rise to intraspecies chimeras embodying functional spermatozoa, which were solely derived from the microinjected PSCs. Furthermore, microinjection of rat ESCs into Tsc22d3-KO mouse embryos gave rise to viable mouse-rat chimeras that exhibited extensive contribution of rat cells to various tissues and organs. Notably, multiple mouse-rat chimeras showed contribution of rat ESCs to the male germline, solely harboring rat spermatids and spermatozoa that were rat ESC-derived and could fertilize rat oocytes. Collectively, this study reports on a method for exclusive germ cell production of one species in another via blastocyst complementation with PSCs. Implications of this study may extend to development of transgenic rat gametes in sterile mice and could further assist efforts to generate germ cells from endangered animal species.

2022-08-01 | GSE203350 | GEO

Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells [scRNAseq_mouse]

2022-08-01 | GSE167434 | GEO

Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells [bulk RNA-seq]

2022-08-01 | GSE167433 | GEO

Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells

Project description:Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells

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Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells [scRNAseq_mouse]

Project description:Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells [scRNAseq_mouse]

| PRJNA704651 | ENA

Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells [scRNAseq_chimera]

Project description:Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells [scRNAseq_chimera]

| PRJNA837067 | ENA

Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells [scRNAseq_rat]

Project description:Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells [scRNAseq_rat]

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Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells [bulk RNA-seq]

Project description:Generation of functional rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells [bulk RNA-seq]

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Generation of functional lungs via conditional blastocyst complementation using pluripotent stem cells.

Project description:Millions of people worldwide with incurable end-stage lung disease die because of inadequate treatment options and limited availability of donor organs for lung transplantation1. Current bioengineering strategies to regenerate the lung have not been able to replicate its extraordinary cellular diversity and complex three-dimensional arrangement, which are indispensable for life-sustaining gas exchange2,3. Here we report the successful generation of functional lungs in mice through a conditional blastocyst complementation (CBC) approach that vacates a specific niche in chimeric hosts and allows for initiation of organogenesis by donor mouse pluripotent stem cells (PSCs). We show that wild-type donor PSCs rescued lung formation in genetically defective recipient mouse embryos unable to specify (due to Ctnnb1cnull mutation) or expand (due to Fgfr2cnull mutation) early respiratory endodermal progenitors. Rescued neonates survived into adulthood and had lungs functionally indistinguishable from those of wild-type littermates. Efficient chimera formation and lung complementation required newly developed culture conditions that maintained the developmental potential of the donor PSCs and were associated with global DNA hypomethylation and increased H4 histone acetylation. These results pave the way for the development of new strategies for generating lungs in large animals to enable modeling of human lung disease as well as cell-based therapeutic interventions4-6.

| S-EPMC9169232 | biostudies-literature

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