Abstract: A tyrosine phosphatase sigma (PTPsigma)-Fc fusion protein comprises a PTPsigma-derived protein and an immunoglobulin (Ig)-derived Fc domain, which can inhibit the signal transduction of PTPsigma by blocking the interaction of the extracellular domain of PTPsigma with a ligand. The PTPsigma-Fc fusion protein inhibits PTPsigma-mediated signaling and as such, can promote the growth of blood stem cells, and can be used for preventing or treating PTPsigma-mediated diseases. Controlling the signal transduction of PTPsigma by utilizing interaction between proteins, the PTPsigma-Fc fusion protein can overcome the problems of conventional inhibitors targeting the active site of PTP. In addition, the solubility of the fusion protein in an aqueous solution can be improved by introducing a mutation thereinto, which makes it possible to apply a high dose to the treatment of the human body and animals.