Hematopoietic cells represent an attractive starting cell type for induced pluripotent stem (iPS) cells induction, yet the molecular mechanisms in hematopoietic reprogramming are poorly defined. In this study, we showed that long-term hematopoietic stem cells are more amenable for iPS cells induction among several hematopoietic stem and progenitor cell (HSPC) populations, and that this is accompanied by an earlier induction of the transcriptional program that is involved in the promotion of macromolecule metabolism and cell proliferation. Notably, we identified multiple signaling pathways that exhibited distinct expression patterns in HSPCs compared to that of fibroblasts, which is the most commonly used model for probing the somatic reprogramming process. We further experimentally confirmed the differential requirements of the Wnt/ß-catenin and transforming growth factor-beta (TGF-ß) signaling pathways in these two cell types. These data demonstrate that hematopoietic cells have a cell-type specific transcriptional program and possess unique signaling requirements in the early phase of reprogramming. Overall design: Examine the differential global gene expression among different hematopietic cells in reprogramming. LT-HSC, ST-HSC, MP and fibroblasts were used in this study. Doxcycline addition could induce expression of oct4, sox2, klf4 and c-myc, consequently reprogramming these cells into iPS cells. Hematopietic cells cultured with doxcycline for 0, 2, 4 days were sampled, and samples at the same timepoint without doxcycline were also taken to exclude vast gene expression change in hematopoietic cell in-vitro culture. Fibroblast samples induced by doxcycline for 0, 2, 4 days were also introduced to provide comparism between lineages.