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Identification and characterization of in vitro expanded hematopoietic stem cells.
Che, James L C; Bode, Daniel; Kucinski, Iwo; Cull, Alyssa H; Bain, Fiona; Becker, Hans J; Jassinskaja, Maria; Barile, Melania; Boyd, Grace; Belmonte, Miriam; Zeng, Andy G X; Igarashi, Kyomi J; Rubio-Lara, Juan; Shepherd, Mairi S; Clay, Anna; Dick, John E; Wilkinson, Adam C; Nakauchi, Hiromitsu; Yamazaki, Satoshi; Göttgens, Berthold; Kent, David G.
Afiliación
  • Che JLC; Wellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Bode D; Department of Haematology, University of Cambridge, Cambridge, UK.
  • Kucinski I; Department of Biology, York Biomedical Research Institute, University of York, York, UK.
  • Cull AH; Wellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Bain F; Department of Haematology, University of Cambridge, Cambridge, UK.
  • Becker HJ; Department of Biology, York Biomedical Research Institute, University of York, York, UK.
  • Jassinskaja M; Wellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Barile M; Department of Haematology, University of Cambridge, Cambridge, UK.
  • Boyd G; Department of Biology, York Biomedical Research Institute, University of York, York, UK.
  • Belmonte M; Department of Biology, York Biomedical Research Institute, University of York, York, UK.
  • Zeng AGX; Division of Stem Cell Biology, Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • Igarashi KJ; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Rubio-Lara J; Department of Biology, York Biomedical Research Institute, University of York, York, UK.
  • Shepherd MS; Wellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Clay A; Department of Haematology, University of Cambridge, Cambridge, UK.
  • Dick JE; Department of Biology, York Biomedical Research Institute, University of York, York, UK.
  • Wilkinson AC; Wellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Nakauchi H; Department of Haematology, University of Cambridge, Cambridge, UK.
  • Yamazaki S; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Göttgens B; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
  • Kent DG; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
EMBO Rep ; 23(10): e55502, 2022 10 06.
Article en En | MEDLINE | ID: mdl-35971894
Hematopoietic stem cells (HSCs) cultured outside the body are the fundamental component of a wide range of cellular and gene therapies. Recent efforts have achieved > 200-fold expansion of functional HSCs, but their molecular characterization has not been possible since the majority of cells are non-HSCs and single cell-initiated cultures have substantial clone-to-clone variability. Using the Fgd5 reporter mouse in combination with the EPCR surface marker, we report exclusive identification of HSCs from non-HSCs in expansion cultures. By directly linking single-clone functional transplantation data with single-clone gene expression profiling, we show that the molecular profile of expanded HSCs is similar to proliferating fetal HSCs and reveals a gene expression signature, including Esam, Prdm16, Fstl1, and Palld, that can identify functional HSCs from multiple cellular states. This "repopulation signature" (RepopSig) also enriches for HSCs in human datasets. Together, these findings demonstrate the power of integrating functional and molecular datasets to better derive meaningful gene signatures and opens the opportunity for a wide range of functional screening and molecular experiments previously not possible due to limited HSC numbers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Relacionadas con la Folistatina Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Relacionadas con la Folistatina Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido