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

Jonah Riddell, Roi Gazit, Brian S. Garrison, Guoji Guo, Assieh Saadatpour, Pankaj K. Mandal, Wataru Ebina, Pavel Volchkov, Guo Cheng Yuan, Stuart H. Orkin, Derrick J. Rossi

Research output: Contribution to journalArticlepeer-review

240 Scopus citations

Abstract

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

Original languageEnglish
Pages (from-to)549-564
Number of pages16
JournalCell
Volume157
Issue number3
DOIs
StatePublished - 24 Apr 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)

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