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Tag: University of Tsukuba

  • Enhanced stem cell culture boosts genome editing safety

    Enhanced stem cell culture boosts genome editing safety

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    Newswise — Tsukuba, Japan—Hematopoietic stem cells (HSCs) are rare cells found in the bone marrow that produce red blood cells, white blood cells, and platelets. Their correct functioning is indispensable for the growth and health of an organism. Accordingly, defects in the DNA of hematopoietic stem cells (mutations) can cause impaired blood production and severe diseases.

    Gene therapy seeks to treat such types of genetic diseases. A breakthrough technology that has driven the entire field in recent years is gene editing via clustered regularly interspaced palindromic repeats/Cas9 (CRISPR/Cas9). Using this technology, one can modify disease-causing mutations and transplant HSCs with recovered function, potentially curing the disease.

    However, the CRISPR/Cas9 system is not perfect. It only corrects mutations in a small fraction of cells and can introduce new, potentially dangerous mutations into other cells. Therefore, selecting corrected cells before transplantation is crucial.

    In 2019, the research group reported a method of expanding HSCs over a long time period using a polymer-based culture system and cytokines. In response to this problem, the authors have developed a novel culture system using a novel high-molecular-weight polymer. This system facilitates the growth of single HSCs in transplantable cell colonies that achieve high blood-producing capacity after long-time ex vivo culture. After editing a mutation in a murine immune deficiency model, the authors individually grow several hundred HSCs and screen them for clones that contain only the desired edit and are expected to engraft successfully. Using this method, the fraction of successfully corrected HSCs used for transplantation can be increased from 20%-30% to 100% while eliminating potentially dangerous mutations from the graft. We believe that this culture system might contribute to improving the efficiency and safety of genome editing in HSCs.

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    This work was supported by the German Research Foundation (BE 6847/1-1 to H.J.B.), the Japan Society for the Promotion of Science (JSPS; #20K16234 to M.S.J.L., #23K15315 to H.J.B., #21F21108 and #20K21612 to S.Y.), the Kay Kendall Leukaemia Fund (A.C.W.), the Japan Science and Technology Agency (JST; #18071245 to C.C.), and the Japanese Agency for Medical Research and Development (AMED; #21bm0404077h0001 and #21bm0704055h0002 to S.Y.). The D.G.K. laboratory is supported by a Blood Cancer UK Bennett Fellowship (15008), an ERC Starting Grant (ERC-2016-STG-715371), a CR-UK Programme Foundation award (DCRPGF100008), the MRC Mouse Genetics Network Haematopoiesis Cluster (MC_PC_21043), and an MRC-AMED joint award (MR/V005502/1).

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    University of Tsukuba

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  • Family tree secrets: Island tree populations older, more diverse than expected

    Family tree secrets: Island tree populations older, more diverse than expected

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    Newswise — Tsukuba, Japan—It’s often assumed that island plant and animal populations are just the simple, fragile cousins of those on the mainland. But now, researchers from Japan have discovered that island populations may be a lot tougher and more complex than previously thought.

    In a recently published study, a research group led by the University of Tsukuba has revealed that the northernmost island populations of Siebold’s beech, Fagus crenata, are older and genetically more diverse than expected.

    Island and mainland populations often differ as a result of islands’ geographical isolation, which is often assumed to restrict the genetic diversity of their populations. However, a number of studies on land plants have shown that island populations have considerable genetic diversity despite their remoteness, indicating that the processes underlying their diversity are more complex than previously thought.

    “Although many island populations have existed for thousands of years or longer, the origins of some of them are still unknown,” says Professor Yoshiaki Tsuda, the main author of the study. “This includes Japan’s northernmost island populations of the native species F. crenata.”

    The research group investigated populations of F. crenata on Okushiri Island in the Japan Sea, which is thought to have broken away from the mainland in the Middle Pleistocene (the Ice Age, which occurred 2.58 million to 11,700 years ago), and remained separate ever since. The northward spread of this species began on the mainland approximately 6,000 years ago, after the last glacial maximum (LGM). The researchers studied the genetics of the island’s populations and those of nearby regions, and found that the island’s populations had high genetic diversity, and may not have arisen from a single colonization event.

    The Okushiri Island populations had a comparable number of private alleles (genetic sequences that are present in a single population and essentially absent in other populations) to the populations studied on nearby Hokkaido, which points to the existence of relict populations on Okushiri Island. A relict is a population of organisms that was more widespread or more diverse in the past in a restricted area.

    Taken together with palaeoecological and vegetation studies, as well as the island’s geology, these results indicate that F. crenata persisted in cryptic refugia (places where climatically sensitive species can survive regardless of incompatibility with the regional climate) on the island.

    “Our evidence indicates that populations of this species already existed on Okushiri Island prior to the LGM, and persisted there for longer than previously thought,” explains Professor Tsuda. The results of this study contribute to a growing body of evidence that island plant populations are more genetically diverse than previously estimated, which has implications for research and management of island species conservation, and the study of gene flow between island and mainland populations.

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    This study was supported by JSPS KAKENHI (JP17K07852 and JP20K06152) and Core-to-Core Program (Asia-Africa Science Platforms: JPJSCCB20220007) from the Japan Society for the Promotion of Science and the 27th Pro Natura Fund Grant Program from the Pro Natura Foundation Japan.
     

    Original Paper

    The article, “Possible northern persistence of Siebold’s beech, Fagus crenata, at its northernmost distribution limit on an island in Japan Sea: Okushiri Island, Hokkaido,” was published in Frontiers in Plant Science at DOI: 10.3389/fpls.2022.990927

    Correspondence

    Associate Professor TSUDA Yoshiaki
    Faculty of Life and Environmental Sciences, University of Tsukuba

    Related Link

    Faculty of Life and Environmental Sciences
    Sugadaira Research Station, Mountain Science Center

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