Somatic Cell Nuclear Transfer

  • Cibelli, Jose (cellular reprogramming, nuclear transfer, embryonic stem cells)
  • Smith, George (reproduction, ovarian function, stress physiology, functional genomics)

Jose B. Cibelli, Professor
Endowed Chair for Large Animal Biotechnology
Depts. of Animal Science, Physiology, and the College of Veterinary Medicine

Our Cellular Reprogramming Laboratory focuses in two aspects of developmental biology. (1) Nuclear Transfer—Cloning: A number of different laboratories, including our own, have demonstrated that a somatic (body) cell, once fused with an egg, is capable of generating not only stem cells (ref 1) but a whole new organism as well (refs 2-4). Interestingly, we still do not comprehend how this is possible. Our laboratory focuses on understanding the molecular events that lead to the transformation of a somatic nucleus into an embryonic-pluripotent one. Insights into the mechanism of de-differentiation will help us generate cloned animals at optimal efficiency for their use in agriculture and medicine (ref 5). (2) Primate Embryonic Stem Cells: Embryonic stem (ES) cells are capable of maintaining an undifferentiated or ‘pluripotent’ state in vitro. At the same time, by modifying the culture conditions, they can generate daughter cells capable of forming all the tissues in the body. We have demonstrated that somatic cells can be turned into ES cells either by nuclear transfer (cloning; ref 1) or by parthenogenesis (ref 6), and that these cells can later be induced to differentiate into multiple complex tissues (ref 6). In order for us to understand how the state of pluripotency is reached and maintained, ES cells are carefully analyzed at the molecular level. Our challenge is now to learn how to produce these cells without having to relay on eggs (ref 7).

REFERENCES CITED
Cibelli JB, Stice SL, Golueke PJ, et al. (1998) Transgenic bovine chimeric offspring produced from somatic cell-derived stem-like cells. Nat Biotechnol 16: 642-646.

Cibelli JB, Stice SL, Golueke PJ, et al. (1998) Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science 280: 1256-1258.

Lanza RP, Cibelli JB, Blackwell C, et al. (2000) Extension of cell life-span and telomere length in animals cloned from senescent somatic cells [see comments]. Science 288: 665-669.

Lanza RP, Cibelli JB, Faber D, et al. (2001) Cloned cattle can be healthy and normal. Science 294: 1893-1894.

Cibelli JB, Campbell KH, Seidel GE, West MD, Lanza RP. (2002) The health profile of cloned animals. Nat Biotechnol 20: 13-14.

Cibelli JB, Grant KA, Chapman KB, et al. (2002) Parthenogenetic stem cells in nonhuman primates. Science 295: 819.

Cibelli J, Kiessling A, Cunniff K, Richards C, Lanza R, West M. (2001) Somatic Cell Nuclear Transfer in Humans: Pronuclear and Early Embryonic Development. e-biomed: The Journal of Regenerative Medicine Volume 2.

George W. Smith, Professor
Principal Investigator, Molecular Animal Reproduction and Neuroendocrinology Laboratory
Depts. of Animal Science and Physiology

Research efforts in the Molecular Animal Reproduction and Neuroendocrinology Laboratory have focused on investigation of fundamental mechanisms that regulate ovarian function in farm animals and the physiological and neuroendocrine mechanisms involved in regulation of the stress response. We have obtained new insight into the hormonal regulation and regulatory role of members of the matrix metalloproteinase gene family in control of follicle rupture and the hormonal regulation and physiological role of various components of the corticotropin releasing factor (CRF) system in promoting the stress response. Recent research efforts also utilize functional genomics approaches to identify specific components of the oocyte transcriptome [catalog of genes expressed in the female germ cell] that play a key role in regulation of folliculogenesis, oocyte function and early embryonic development, and to identify objective molecular markers that are predictive of oocyte competence and subsequent potential reproductive success post-fertilization.