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Patrick S Western

Publications and source records attributed to Patrick S Western.

3 recordsLinked to original sources
PubMed2026

Handle with care: packaging the oocyte epigenome for the next generation.

During oocyte growth, substantial epigenetic programming occurs to establish a distinctive epigenome including appropriately patterned DNA methylation and histone modifications. Oocyte epigenetic programming must be tightly spatiotemporally regulated to ensure that a wide variety of epigenetic modifiers correctly establish their respective modifications to mediate precise control of gene expression. Furthermore, epigenetic modifications in oocytes include canonical and non-canonical genomic imprints, which are transmitted through meiosis to offspring. Significantly, disruptions in oocyte epigenetic programming can cause aberrant developmental outcomes in the next generation mediated by altered imprinting. Polycomb repressive complex 2 is an important epigenetic modifier that establishes histone 3 lysine 27 trimethylation and non-canonical imprints during mouse oogenesis, which are important for normal offspring development. While it is widely recognised that altered oocyte epigenetic programming can disrupt offspring development, mechanisms controlling maternal epigenetic inheritance remain poorly understood. The possibility remains that non-canonical imprinting exists in humans, although this requires confirmation. This review discusses mouse and human oocyte epigenetic programming including interactions between various epigenetic modifiers and modifications that form the unique oocyte epigenome. Understanding how oocyte epigenetic programming is regulated will be crucial in discerning how changes to the oocyte epigenome can disrupt epigenetic memory and alter developmental outcomes in offspring.

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PubMed2003

Nuclei of adult mammalian somatic cells are directly reprogrammed to oct-4 stem cell gene expression by amphibian oocytes.

Nuclear reprogramming by the transplantation of somatic cell nuclei to eggs (in second meiotic metaphase) is always followed by a phase of chromosome replication and cell division before new gene expression is seen. To help understand the mechanism of nuclear reprogramming, we have asked whether the nuclei of normal, nontransformed, nondividing, and terminally differentiated mammalian cells can be directly reprogrammed, without DNA replication, by Xenopus oocytes. We find that nuclei of adult mouse thymocytes and of adult human blood lymphocytes, injected into Xenopus oocytes, are induced to extinguish a differentiation marker and to strongly express oct-4, the most diagnostic mammalian stem cell/pluripotency marker. In the course of 2 days at 18 degrees C, the mammalian oct-4 transcripts are spliced to mature mRNA. We conclude that normal mammalian nuclei can be directly reprogrammed by the nucleus (germinal vesicle) of amphibian oocytes to express oct-4 at a rate comparable to that of oct-4 in mouse ES cells. To our knowledge, this is the first demonstration of a stem cell marker being induced in a differentiated adult human cell nucleus. This is an early step toward the long-term aim of developing a procedure for reprogramming readily accessible human adult cells for cell replacement therapy.

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