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- All Subjects: Stem Cells
- Creators: Philbrick, Samuel
Agassiz’s desert tortoise (Gopherus agassizii) is a long-lived species native to the Mojave Desert and is listed as threatened under the US Endangered Species Act. To aid conservation efforts for preserving the genetic diversity of this species, we generated a whole genome reference sequence with an annotation based on deep transcriptome sequences of adult skeletal muscle, lung, brain, and blood. The draft genome assembly for G. agassizii has a scaffold N50 length of 252 kbp and a total length of 2.4 Gbp. Genome annotation reveals 20,172 protein-coding genes in the G. agassizii assembly, and that gene structure is more similar to chicken than other turtles. We provide a series of comparative analyses demonstrating (1) that turtles are among the slowest-evolving genome-enabled reptiles, (2) amino acid changes in genes controlling desert tortoise traits such as shell development, longevity and osmoregulation, and (3) fixed variants across the Gopherus species complex in genes related to desert adaptations, including circadian rhythm and innate immune response. This G. agassizii genome reference and annotation is the first such resource for any tortoise, and will serve as a foundation for future analysis of the genetic basis of adaptations to the desert environment, allow for investigation into genomic factors affecting tortoise health, disease and longevity, and serve as a valuable resource for additional studies in this species complex.
Data Availability: All genomic and transcriptomic sequence files are available from the NIH-NCBI BioProject database (accession numbers PRJNA352725, PRJNA352726, and PRJNA281763). All genome assembly, transcriptome assembly, predicted protein, transcript, genome annotation, repeatmasker, phylogenetic trees, .vcf and GO enrichment files are available on Harvard Dataverse (doi:10.7910/DVN/EH2S9K).
Human pluripotent stem cells are valued for their potential to form numerous specialized cells and for their longevity. In the US, where a portion of the population is opposed to destruction of human embryos to obtain stem cells, what avenues are open to scientists for obtaining pluripotent cells that do not offend the moral sensibilities of a significant number of citizens? It is this question that the official position paper, or white paper, "Alternative Sources of Human Pluripotent Stem Cells," published in May 2005 by the President's Council on Bioethics under the chairmanship of Leon Kass, seeks to answer. Three experts external to the council, Andrew Fire from the Stanford University School of Medicine, Markus Grompe of the Oregon Health and Science University, and Janet Rossant from the Samuel Lunenfeld Research Institute in Toronto, also reviewed the white paper prior to publication.
On 9 August 2001, US President George W. Bush gave an eleven-minute speech from his ranch in Crawford, Texas, on the ethics and fate of federal funding for stem cell research. Bush also announced the creation of a special council to oversee stem cell research. In the speech President Bush acknowledged the importance of issues surrounding stem cell research to many Americans, presented different arguments in favor of and opposing embryonic stem cell research, and explained his decision to limit but not completely eliminate potential federal funding for embryonic stem cell (ESC) research. The speech was important to embryology as a field because it determined the US government's policy on funding human ESC research for the eight years of George W. Bush's administration.
Induced pluripotent stem cells (iPSCs) are studied carefully by scientists not just because they are a potential source of stem cells that circumvents ethical controversy involved with experimentation on human embryos, but also because of their unique potential to advance the field of regenerative medicine. First generated in a lab by Kazutoshi Takahashi and Shinya Yamanaka in 2006, iPSCs have the ability to differentiate into cells of all types. If scientists discover how to induce differentiated cells to return to a pluripotent state using a method that leaves the iPSCs safe for transplantation, then patients could receive stem cell transplants with cells containing their own DNA. This would presumably remove the danger of transplant rejection that comes with foreign cell transplantation.
Shinya Yamanaka gained international prominence after publishing articles detailing the successful generation of induced pluripotent stem (iPS) cells, first in mice, then in humans. Yamanaka induced somatic cells to act like human embryonic stem cells (hESCs), allowing researchers to experiment with non-embryonic stem cells with a similar capacity as hESCs. The research involving iPS cells therefore offered new potential for research and application in medical treatment, without many of the ethical objections that hESC research entailed.
In the July 2007 issue of Nature, Keisuke Okita, Tomoko Ichisaka, and Shinya Yamanaka added to the new work on induced pluripotent stem cells (iPSCs) with their "Generation of Germline-Competent Induced Pluripotent Stem Cells" (henceforth abbreviated "Generation"). The authors begin the paper by noting their desire to find a method for inducing somatic cells of patients to return to a pluripotent state, a state from which the cell can differentiate into any type of tissue but cannot form an entire organism. If this is made possible, the authors claim, the ethical controversy surrounding the use of embryonic stem cells (ES cells) and the dangers of patient rejection of donated ES cells could be bypassed completely.
In November 2007, Masato Nakagawa, along with a number of other researchers including Kazutoshi Takahashi, Keisuke Okita, and Shinya Yamanaka, published "Generation of Induced Pluripotent Stem Cells without Myc from Mouse and Human Fibroblasts" (abbreviated "Generation") in Nature. In "Generation," the authors point to dedifferentiation of somatic cells as an avenue for generating pluripotent stem cells useful for treating specific patients and diseases. They provide background to their research by observing that previous attempts to reprogram somatic cells to a state of greater differentiability with retroviral factors Oct3/4, Sox2, c-Myc, and Klf4 had succeeded in producing induced pluripotent stem (iPS) cells that contributed to viable adult chimeras and possessed germline competency. However, as they note, the c-Myc retrovirus contributes to tumors in generated chimeras, rendering iPS cells produced with c-Myc useless for clinical applications. The authors attempt to overcome this problem by modifying the standard protocol for producing iPS cells in mice in such a way that the c-Myc retrovirus is removed. They identify problems and benefits associated with this method, but most importantly note that their method generated iPS cells that did not cause tumors in chimeric mice. Nakagawa and colleagues also report that they successfully reprogrammed adult dermal fibroblasts to return to a pluripotent state without c-Myc.