Nuclear Reprogramming in Cells
J. B. Gurdon1 and
D. A. Melton2
1 Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Zoology, University of Cambridge, Cambridge CB2 12N, UK.
2 Molecular and Cellular Biology, Harvard/Howard Hughes Medical Institute (HHMI), Cambridge, MA 02138, USA.
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Fig. 1. Designs of nuclear transfer experiments (A) to unfertilized eggs (second meiotic metaphase) of frogs or mammals or (B) to first meiotic frog oocytes. (A) and (B) show the transfer of somatic cell nuclei. (C) Design of cell fusion experiments.
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Fig. 3. Nuclei enlarge and chromatin decondenses during nuclear reprogramming. (A) A chick erythrocyte 1 hour (left) and 2 days (right) after fusion to a human HeLa cell (17). The dotted lines indicate the outside of the fused hybrid cells. The smaller nucleus is that of the chick erythrocyte. [Adapted with permission from (17)] (B) Mouse ES cell nuclei immediately (left) and 2 days (right) after injection into an amphibian oocyte germinal vesicle (9). The injected nuclei have enlarged about 30 times in volume.
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Fig. 4. Chromosomal protein exchange in a normal cell (left) or after nuclear transfer to an egg or oocyte (right). Yellow indicates donor-cell nuclear proteins that maintain gene expression. Blue indicates egg nuclear proteins that replace somatic proteins lost by dilution and that induce new gene expression.
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Fig. 5. Four experimental routes for nuclear reprogramming. Blue components represent the normal process of cell differentiation during development from a fertilized egg to adult cells or tissues. Red arrows represent nuclear reprogramming (A) by nuclear transfer to eggs, (B) by induced pluripotency iPS, (C) by lineage switching back to a branch point and out again in a different direction, and (D) by direct conversion. The lower part of the figure shows reprogramming by the generation of ES cells; these can be aggregated into an embryoid body (EB), made to differentiate in culture (diff), or transplanted to a blastocyst. In each case, various types of adult cells can be formed.
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