Robert H. Blelloch *, Konrad Hochedlinger *, Yasuhiro Yamada *, Cameron Brennan , Minjung Kim , Beatrice Mintz ¶, Lynda Chin , and Rudolf Jaenisch *|| ^@

*Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
||Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;
¹ Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115;
² Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115; and
¶Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111

R.H.B. and K.H. contributed equally to this work.
^@To whom correspondence should be addressed.
Rudolf Jaenisch, E-mail:   jaenisch@wi.mit.edu

Embryonal carcinoma (EC) cells have served as a model to study the relationship between cancer and cellular differentiation given their potential to produce tumors and, to varying degrees, participate in
embryonic development. Here, nuclear transplantation was used to assess the extent to which the tumorigenic and developmental potential of EC cells is governed by epigenetic as opposed to genetic
alterations. Nuclei from three independent mouse EC cell lines (F9, P19, and METT-1) with differing developmental and tumorigenic potentials all were able to direct early embryo development, producing morphologically normal blastocysts that gave rise to nuclear transfer (NT)-derived embryonic stem (ES) cell lines at a high efficiency. However, when tested for tumor or chimera formation, the resulting NT ES cells
displayed an identical potential as their respective donor EC cells, in stark contrast to previously reported NT ES cells derived from transfer of untransformed cells. Consistent with this finding, comparative genomic hybridization identified previously undescribed genetic lesions in the EC cell lines. Therefore, nonreprogrammable genetic modifications within EC nuclei define the developmental and tumorigenic potential of resulting NT ES cells. Our findings support the notion that cancer results from the deregulation of stem cells and further suggest that the genetics of ECs will reveal genes involved in stem cell self-renewal and pluripotency.

1. Hochedlinger K, Blelloch R, Brennan C, Yamada Y, Kim M, Chin L, and Jaenisch R, "Reprogramming of a melanoma genome by nuclear transplantation".

2. Frenster JH, and Hovsepian JA, "Activator RNA Exchange during Interphase Chromatin Reprogramming".

3. Links to Reprogramming and Neoplasia:

Links to Euchromatin Activator RNA Reviews:
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Links to Ultrastructural Probes of DNase I-Sensitive Sites:
Links to RNA as a Therapeutic Agent:
Links to Hodgkin Lymphoma Immuno-Pathology:
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Links to Selective Gene Transcription:
Links to RNA-Induced Epigenetics:
Links to RNA-Induced Embryogenesis:
Links to RNA and Biological Causality:
Links to Reprogramming and Neoplasia:

"Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA".

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