Reprogramming stem cells is a microenvironmental task

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That tumor cells for all practical purposes are unstable and plastic could be expected. However, the astonishing ability of the nuclei from cells of normal adult tissues to be reprogrammed - given the right embryonic context - found its final truth even for mammals in the experiments that allowed engineering Dolly (1). The landmark experiments showed that nuclei originating from cells of frozen mammary tissues were capable of being reprogrammed by the embryonic cytoplasm and its microenvironment to produce a normal sheep. The rest is history. However, whether microenvironments other than those of the embryos can also reprogram adult cells ... continued below

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Bissell, Mina J & Inman, Jamie October 14, 2008.

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That tumor cells for all practical purposes are unstable and plastic could be expected. However, the astonishing ability of the nuclei from cells of normal adult tissues to be reprogrammed - given the right embryonic context - found its final truth even for mammals in the experiments that allowed engineering Dolly (1). The landmark experiments showed that nuclei originating from cells of frozen mammary tissues were capable of being reprogrammed by the embryonic cytoplasm and its microenvironment to produce a normal sheep. The rest is history. However, whether microenvironments other than those of the embryos can also reprogram adult cells of different tissue origins still containing their cytoplasm is of obvious interest. In this issue of PNAS, the laboratory of Gilbert Smith (2) reports on how the mammary gland microenvironment can reprogram both embryonic and adult stem neuronal cells. The work is a follow-up to their previous report on testis stem cells that were reprogrammed by the mammary microenvironment (3). They demonstrated that cells isolated from the seminiferous tubules of the mature testis, mixed with normal mammary epithelial cells, contributed a sizable number of epithelial progeny to normal mammary outgrowths in transplanted mammary fat pads. However, in those experiments they were unable to distinguish which subpopulation of the testis cells contributed progeny to the mammary epithelial tree. The current work adds new, compelling, and provocative information to our understanding of stem cell plasticity. Booth et al. (2) use neuronal stem cells (NSCs) isolated from WAP-cre/R26R mice combined with unlabeled mammary epithelial cells that subsequently are implanted in cleared mammary fat pads. In this new microenvironment, the NSCs that are incorporated into the branching mammary tree make chimeric glands (Fig. 1) that remarkably can also express the milk protein {beta}-casein, progesterone receptor, and estrogen receptor {alpha}. Remarkably, the primary transplants are capable of maintaining chimerism through serial transplantation. When the chimeric glands are explanted back into NSC growth media, cells with NSC markers were present only in explants from the first transplant and not from explants in the subsequent serial transplants, suggesting that there is a window of time and an unknown but specific context for becoming NSC again.

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  • Journal Name: Proceedings of the National Academy of Sciences; Journal Volume: 105; Journal Issue: 41; Related Information: Journal Publication Date: 10/14/2008

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  • Report No.: LBNL-4095E
  • Grant Number: DE-AC02-05CH11231
  • Grant Number: CA 126552, CA 064786, CA 112970, CA057621, CA 143836, CA143233
  • DOI: 10.1073/pnas.0808457105 | External Link
  • Office of Scientific & Technical Information Report Number: 1000965
  • Archival Resource Key: ark:/67531/metadc843292

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Reports, articles and other documents harvested from the Office of Scientific and Technical Information.

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  • October 14, 2008

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  • May 19, 2016, 3:16 p.m.

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  • June 15, 2016, 9:36 p.m.

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Bissell, Mina J & Inman, Jamie. Reprogramming stem cells is a microenvironmental task, article, October 14, 2008; Berkeley, California. (digital.library.unt.edu/ark:/67531/metadc843292/: accessed October 20, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.