Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors

作者: Jonah Riddell , Roi Gazit , Brian S. Garrison , Guoji Guo , Assieh Saadatpour

DOI: 10.1016/J.CELL.2014.04.006

关键词: Cell biologyHaematopoiesisImmunologyEndothelial stem cellHematopoietic stem cell transplantationMyeloidBiologyStem cellTransplantationReprogrammingProgenitor cell

摘要: Hematopoietic stem cells (HSCs) sustain blood formation throughout life and are the functional units of bone marrow transplantation. We show that transient expression six transcription factors Run1t1, Hlf, Lmo2, Prdm5, Pbx1, Zfp37 imparts multilineage transplantation potential onto otherwise committed lymphoid myeloid progenitors effector cells. Inclusion Mycn Meis1 use polycistronic viruses increase reprogramming efficacy. The reprogrammed cells, designated induced-HSCs (iHSCs), possess clonal differentiation potential, reconstitute stem/progenitor compartments, serially transplantable. Single-cell analysis revealed iHSCs derived under optimal conditions exhibit a gene profile is highly similar to endogenous HSCs. These findings demonstrate set defined sufficient activate networks governing HSC identity in Our results raise prospect cell may be strategy for derivation transplantable clinical application.

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