We have recently been engaged in studies of epigenetic programming and gene expression associated with specification of foundational spermatogonial stem cells. This image shows a tSNE plot of single-cell RNA seq data revealing 12 different cell subpopulations among spermatogonia in the developing testis.
This image shows a 3D representation of the relative similarity between the transcriptomes of germ cells types throughout development and spermatogenesis. Implementation of novel bioinformatics techniques has allowed our lab to study the transcriptional makeup of these individual cell populations with a much higher resolution that what was possible in the past.
We have shared leadership of an effort to develop the baboon as a clinically relevant animal model for studies of the efficacy and safety of cell-based therapies. This image shows a heatmap displaying hierarchical clustering of transcriptional similarities between iPSC and ES cells obtained from baboon, human, and mouse origins.
Our previous work conducted primarily in the ‘pre-genomics’ era was among the very first to characterize spermatogenesis-specific gene expression when genes were examined one at a time. Our discovery of the intronless structure of the human PGK2 gene established a novel paradigm for the origin of new functional genes by gene duplication via retroposition. These and related studies provided a critical foundation for our understanding of how tissue-, cell type-, and developmental stage-specific transcription of genes is regulated in the germ line, and this has served as a foundation for our ongoing genome-wide studies to profile the transcriptome and epigenome of developing and differentiating germ cells and stem cells.
Building off of past work, we utilize various staining techniques including DNA and RNA fluorescence in situ hybridization (FISH) to better understand gene expression during spermatogenesis.
We study a wide range of different cell types and cell lines. This image shows mouse embryonic stem cells (mESCs) grown in 2i LIF conditions free of feeder cells and stained for classical mouse embryonic stem cell markers. We are continuing to examine cell-type or epigenetic state-specific differences in levels of maintenance of integrity of the genome and the epigenome.
Research in the McCarrey lab is centered on mammalian germ cells and stem cells. Experimental models include the mouse, baboon, and human samples. We are interested in the epigenetic regulation of cell functions, including determination of cell fate, maintenance of genetic integrity, regulation of gene expression, and epigenomic reprogramming in the embryo and germ lines, including genomic imprinting. We are also interested in disruption of normal epigenetic programming (epimutations) caused by either methods of assisted reproduction, environmental exposures, or adverse lifestyles, and the potential for these induced epimutations to be transmitted to subsequent generations by transgenerational epigenetic inheritance. Finally we are interested in the evolution of tissue-specific gene expression in mammalian species, and developing the baboon as a model system for testing stem cell-based therapeutic applications.
Inquiries regarding opportunities for graduate student or postdoctoral positions can be addressed to email@example.com.
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