The pursuit of ES cell lines of domesticated ungulates

Authors: Talbot, Neil; Blomberg, Le Ann

Submitted to: Stem Cell Review
Publication Type: Review Article
Publication Acceptance Date: 5/3/2008
Publication Date: 7/9/2008
Citation: Talbot, N.C., Blomberg, L.A. 2008. The pursuit of ES cell lines of domesticated ungulates. Stem Cell Reviews. 4(3):235-254.

Interpretive Summary: In contrast to adult body cells, embryonic stem (ES) cells maintain an undifferentiated state, that is, they have the ability to give rise, or “differentiate” into all the cells of the body, including egg and sperm. These characteristics make ES cell lines important resources for the advancement of human medicine, and, if established for domesticated ungulates, would help make possible the improvement of farm animals through their contribution to genetic engineering technology. Unfortunately, despite significant advances in our understanding of human and mouse ES cells, the establishment of ES cell lines from economically important ungulate species, such as the pig, sheep, and cow, has been unsuccessful to date. This may result from a lack of understanding of species-specific mechanisms that promote or influence cell “pluripotency” or “stemness”, that is, the ability to give rise to all the different types of cells in the body. Thorough molecular characterization of the early pig and cow embryo cells from which ES cell lines could be made needs to be done to provide species-appropriate pluripotency markers. Also, recent new knowledge and new techniques in the creation and maintenance of mouse and human ES cells should greatly improve the chances of developing efficient, reproducible methods for making ES cell lines of the pig, cow, goat, sheep and horse.

Technical Abstract: In contrast to differentiated cells, embryonic stem cells (ESC) maintain an undifferentiated state, have the ability to self-renew, and exhibit pluripotency, i.e., they can give rise to most if not all somatic cell types and to the germ cells, egg and sperm. These characteristics make ES cell lines important resources for the advancement of human regenerative medicine, and, if established for domesticated ungulates, would help make possible the improvement of farm animals through their contribution to genetic engineering technology. Combining other genetic engineering technologies, such as somatic cell nuclear transfer (SCNT) with ESC technology may result in synergistic gains in the ability to precisely make and study genetic alterations in mammals. Unfortunately, despite significant advances in our understanding of human and mouse ESC, the derivation of ES cell lines from ungulate species has been unsuccessful. This may result from a lack of understanding of species-specific mechanisms that promote or influence cell pluripotency. Thorough molecular characterizations, including the elucidation of stem cell “marker” signaling cascade hierarchy, species-appropriate pluripotency markers, and pluripotency-associated chromatin alterations in the genomes of ungulate species, should improve the chances of developing efficient, reproducible technologies for the establishment of ES cell lines of economically important species like the pig, cow, goat, sheep and horse.