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Targeted Application of Human Genetic Variation Can Improve Red Blood Cell Production from Stem Cells.
Giani, Felix C; Fiorini, Claudia; Wakabayashi, Aoi; Ludwig, Leif S; Salem, Rany M; Jobaliya, Chintan D; Regan, Stephanie N; Ulirsch, Jacob C; Liang, Ge; Steinberg-Shemer, Orna; Guo, Michael H; Esko, Tõnu; Tong, Wei; Brugnara, Carlo; Hirschhorn, Joel N; Weiss, Mitchell J; Zon, Leonard I; Chou, Stella T; French, Deborah L; Musunuru, Kiran; Sankaran, Vijay G.
Afiliación
  • Giani FC; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Fiorini C; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Wakabayashi A; Department of Neonatology, Charité-Universitätsmedizin Berlin, Berlin 10117, Germany.
  • Ludwig LS; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Salem RM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Jobaliya CD; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Regan SN; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ulirsch JC; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Liang G; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Steinberg-Shemer O; Department of Neonatology, Charité-Universitätsmedizin Berlin, Berlin 10117, Germany.
  • Guo MH; Institute for Chemistry and Biochemistry, Freie Universität Berlin, Berlin 14195, Germany.
  • Esko T; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Tong W; Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Brugnara C; Departments of Pathology and Laboratory Medicine and Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Hirschhorn JN; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Weiss MJ; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Zon LI; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Chou ST; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • French DL; Departments of Pathology and Laboratory Medicine and Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Musunuru K; Departments of Pathology and Laboratory Medicine and Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Sankaran VG; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell Stem Cell ; 18(1): 73-78, 2016 Jan 07.
Article en En | MEDLINE | ID: mdl-26607381
Multipotent and pluripotent stem cells are potential sources for cell and tissue replacement therapies. For example, stem cell-derived red blood cells (RBCs) are a potential alternative to donated blood, but yield and quality remain a challenge. Here, we show that application of insight from human population genetic studies can enhance RBC production from stem cells. The SH2B3 gene encodes a negative regulator of cytokine signaling and naturally occurring loss-of-function variants in this gene increase RBC counts in vivo. Targeted suppression of SH2B3 in primary human hematopoietic stem and progenitor cells enhanced the maturation and overall yield of in-vitro-derived RBCs. Moreover, inactivation of SH2B3 by CRISPR/Cas9 genome editing in human pluripotent stem cells allowed enhanced erythroid cell expansion with preserved differentiation. Our findings therefore highlight the potential for combining human genome variation studies with genome editing approaches to improve cell and tissue production for regenerative medicine.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre / Eritrocitos Límite: Humans Idioma: En Revista: Cell Stem Cell Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre / Eritrocitos Límite: Humans Idioma: En Revista: Cell Stem Cell Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos