Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation
A specialized bone marrow microenvironment (niche) regulates hematopoietic stem cell (HSC) self-renewal and commitment. For successful donor-HSC engraftment, the niche must be emptied via myeloablative irradiation or chemotherapy. However, myeloablation can cause severe complications and even mortal...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2016-12, Vol.354 (6316), p.1152-1155 |
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| creator | Taya, Yuki Ota, Yasunori Wilkinson, Adam C. Kanazawa, Ayano Watarai, Hiroshi Kasai, Masataka Nakauchi, Hiromitsu Yamazaki, Satoshi |
| description | A specialized bone marrow microenvironment (niche) regulates hematopoietic stem cell (HSC) self-renewal and commitment. For successful donor-HSC engraftment, the niche must be emptied via myeloablative irradiation or chemotherapy. However, myeloablation can cause severe complications and even mortality. Here we report that the essential amino acid valine is indispensable for the proliferation and maintenance of HSCs. Both mouse and human HSCs failed to proliferate when cultured in valine-depleted conditions. In mice fed a valine-restricted diet, HSC frequency fell dramatically within 1 week. Furthermore, dietary valine restriction emptied the mouse bone marrow niche and afforded donor-HSC engraftment without chemoirradiative myeloablation. These findings indicate a critical role for valine in HSC maintenance and suggest that dietary valine restriction may reduce iatrogenic complications in HSC transplantation. |
| doi_str_mv | 10.1126/science.aag3145 |
| format | Article |
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For successful donor-HSC engraftment, the niche must be emptied via myeloablative irradiation or chemotherapy. However, myeloablation can cause severe complications and even mortality. Here we report that the essential amino acid valine is indispensable for the proliferation and maintenance of HSCs. Both mouse and human HSCs failed to proliferate when cultured in valine-depleted conditions. In mice fed a valine-restricted diet, HSC frequency fell dramatically within 1 week. Furthermore, dietary valine restriction emptied the mouse bone marrow niche and afforded donor-HSC engraftment without chemoirradiative myeloablation. 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These findings indicate a critical role for valine in HSC maintenance and suggest that dietary valine restriction may reduce iatrogenic complications in HSC transplantation.</description><subject>Amino acids</subject><subject>Animals</subject><subject>Blood</subject><subject>Bone marrow</subject><subject>Cell Proliferation</subject><subject>Constrictions</subject><subject>Cysteine - deficiency</subject><subject>Diet</subject><subject>Female</subject><subject>Hematopoiesis - physiology</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Hematopoietic Stem Cells - physiology</subject><subject>Hierarchies</subject><subject>Humans</subject><subject>Iatrogenic Disease</subject><subject>Maintenance</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Stem Cell Niche - physiology</subject><subject>Stem cells</subject><subject>Transplantation</subject><subject>Valine</subject><subject>Valine - deficiency</subject><subject>Valine - 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deficiency</topic><topic>Diet</topic><topic>Female</topic><topic>Hematopoiesis - physiology</topic><topic>Hematopoietic Stem Cell Transplantation - adverse effects</topic><topic>Hematopoietic Stem Cells - physiology</topic><topic>Hierarchies</topic><topic>Humans</topic><topic>Iatrogenic Disease</topic><topic>Maintenance</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Stem Cell Niche - physiology</topic><topic>Stem cells</topic><topic>Transplantation</topic><topic>Valine</topic><topic>Valine - deficiency</topic><topic>Valine - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Taya, Yuki</creatorcontrib><creatorcontrib>Ota, Yasunori</creatorcontrib><creatorcontrib>Wilkinson, Adam C.</creatorcontrib><creatorcontrib>Kanazawa, Ayano</creatorcontrib><creatorcontrib>Watarai, Hiroshi</creatorcontrib><creatorcontrib>Kasai, Masataka</creatorcontrib><creatorcontrib>Nakauchi, Hiromitsu</creatorcontrib><creatorcontrib>Yamazaki, Satoshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taya, Yuki</au><au>Ota, Yasunori</au><au>Wilkinson, Adam C.</au><au>Kanazawa, Ayano</au><au>Watarai, Hiroshi</au><au>Kasai, Masataka</au><au>Nakauchi, Hiromitsu</au><au>Yamazaki, Satoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2016-12-02</date><risdate>2016</risdate><volume>354</volume><issue>6316</issue><spage>1152</spage><epage>1155</epage><pages>1152-1155</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>A specialized bone marrow microenvironment (niche) regulates hematopoietic stem cell (HSC) self-renewal and commitment. For successful donor-HSC engraftment, the niche must be emptied via myeloablative irradiation or chemotherapy. However, myeloablation can cause severe complications and even mortality. Here we report that the essential amino acid valine is indispensable for the proliferation and maintenance of HSCs. Both mouse and human HSCs failed to proliferate when cultured in valine-depleted conditions. In mice fed a valine-restricted diet, HSC frequency fell dramatically within 1 week. Furthermore, dietary valine restriction emptied the mouse bone marrow niche and afforded donor-HSC engraftment without chemoirradiative myeloablation. These findings indicate a critical role for valine in HSC maintenance and suggest that dietary valine restriction may reduce iatrogenic complications in HSC transplantation.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>27934766</pmid><doi>10.1126/science.aag3145</doi><tpages>4</tpages></addata></record> |
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| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2016-12, Vol.354 (6316), p.1152-1155 |
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| subjects | Amino acids Animals Blood Bone marrow Cell Proliferation Constrictions Cysteine - deficiency Diet Female Hematopoiesis - physiology Hematopoietic Stem Cell Transplantation - adverse effects Hematopoietic Stem Cells - physiology Hierarchies Humans Iatrogenic Disease Maintenance Metabolism Mice Mice, Inbred C57BL Stem Cell Niche - physiology Stem cells Transplantation Valine Valine - deficiency Valine - physiology |
| title | Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation |
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