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nWithin the hematopoietic system, Hematopoietic stem cells (HSCs) are the only cells with the functional capacity to differen-cells can be derived from patient cells, thereby putting autolo-gous cell-based therapies within reach if HSCs can be success-fully generated. However, despite considerable progress intiate to all blood lineages, and to self-renew for life. These prop-erties, in combination with the ability of HSCs to engraft condi-defining the developmental pathways leading to HSCs from pluripotent cells (Sturgeon et al., 2013), the generation ofRun1t1, 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 reprogram-ming efficacy. The reprogrammed cells, designated induced-HSCs (iHSCs), possess clonal multilineage differentiation potential, reconstitute stem/progeni-tor compartments, and are serially transplantable. Single-cell analysis revealed that iHSCs derived un-der 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