Cloning with differentiated cells

Adult stem cells are not required to clone mice from somatic cells, according to a new study published online in Nature Genetics. Using somatic cell nuclear transfer (SCNT), researchers cloned mice from fully differentiated blood cells. In vitro studies also suggested that cloning may be easier with these mature cells than with adult stem cells, hinting that adult stem cells may have little in common with embryonic stem (ES) cells, the authors say."Adult stem cells do not have similar advantages to ES cells ," lead author Tao Cheng, of the University of Pittsburgh, told The Scientist. "In my view, an adult stem cell is still quite specialized."Reproductive cloning with embryonic stem cells is much more efficient than cloning with somatic cells, but it's never been shown whether mammalian clones such as Dolly derived from adult stem cells or from differentiated cells, Cheng said.Led by Li-Ying Sung and Shaorong Gao, of the University of Connecticut, the researchers performed SCNT with three different stages of hematopoietic cells as donors: stem cells, progenitor cells, and mature cells called granulocytes. They found that in vitro cloning efficiency through the blastocyst stage of embryogenesis was lowest for stem cells and highest for fully mature cells.The result was a surprise, Cheng said. When his group began the study, "we they thought the stem cells might offer an advantage in cloning," he told The Scientist, but "it turns out it's not the case."The team next used mature granulocytes as donors for embryos that were implanted in surrogate mothers. After more than 1,300 nuclear transfers, around 35% reached the blastocyst stage, and two cloned pups were carried to term. The pups were born alive but died shortly after birth. According to the researchers, their experiments mark the first time that a full-term pup has developed directly from a terminally differentiated cell. Other groups have produced cloned pups from differentiated cells, but only after an intermediate step in which embryonic stem cells derived from nuclear transfer were then used for a second nuclear transfer.Finding that hematopoietic stem cells are less efficient than mature hematopoietic cells at producing cloned blastocysts suggests that adult stem cells may have little in common with embryonic stem cells other than a capacity for self-renewal, Cheng said. But according to Ware of the University of Washington in Seattle, who was not involved in the study, the researchers did not actually show that cloning mice is more efficient with differentiated cells -- only that cloning blastocysts is. That doesn't "necessarily correlate with how many pups you're going to get," she said. The high number of cloned blastocysts that the researchers produced is "potentially very exciting" for future cloning efforts, according to John McCarrey of the University of Texas at San Antonio, who wasn't involved in the research. However, SCNT yields only a small percentage of cloned blastocysts for other types of differentiated cells, he said. The high cloning efficiency of mature blood cells "would appear to be a unique characteristic of those granulocytes... as opposed to a generic characteristic of differentiated cells."It's a mystery why differentiated hematopoietic cells should be more suitable for nuclear transfer than adult stem cells, Cheng said. According to Ware, future studies should look for epigenetic similarities between differentiated cells and ES cells that are not shared by adult stem cells.Melissa Lee Phillips mphillips@the-scientist.comCorrection (posted Oct. 5): When originally posted, this story incorrectly identified Tao Cheng as being with the University of Connecticut. The Scientist regrets the error.Links within this article:R. Lewis, "The Clone Reimagined," The Scientist, April 25, 2005. http://www.the-scientist.com/2005/04/25/13/1/L-Y Sung et al., "Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer," Nature Genetics, published online October 1, 2006. http://www.nature.com/ngC.T. Scott, "Trials of the Heart," The Scientist, July 4, 2005. http://www.the-scientist.com/article/display/15592Tao Cheng http://www.mirm.pitt.edu/people/bios/Cheng1.htmlW.M. Rideout, III, et al., "Nuclear cloning and epigenetic reprogramming of the genome," Science, August 21, 2001. http://www.the-scientist.com/pubmed/11498580K. Hochedlinger, R. Jaenisch, "Nuclear transplantation: lessons from frogs and mice," Current Opinion in Cell Biology, December 2002. http://www.the-scientist.com/pubmed/12473349K. Eggan et al., "Mice cloned from olfactory sensory neurons," Nature, March 4, 2004. http://www.the-scientist.com/pubmed/14990966Carol Ware http://depts.washington.edu/compmed/faculty/ware.htmJohn McCarrey http://bio.utsa.edu/faculty/mccarrey.html

Cloning with differentiated cells

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