HoxB4+ Degradation-Resistant Cell-Penetrating Protein (50 ug)
HoxB4 gain-of-function has been demonstrated to increase the proliferative capacity of Hematopoietic Stem Cells (HSCs) of both mice and humans, without forcing differentiation. HSCs cultured with HoxB4 or forced to overexpress HoxB4 proliferate rapidly and maintain markers of long-term repopulating HSCs. HoxB4-treated murine and human HSCs exhibit superior chimerism across hematopoietic lineages in primary and secondary HSC transplant studies. Human and murine HoxB4 sequences are generally functional across species.
TAT-HoxB4+ has been explicitly shown in vitro and in vivo to outperform wildtype HoxB4.
Lee J, Shieh JH, Zhang J, Liu L, Zhang Y, Eom JY, Morrone G, Moore MA, Zhou P. Improved ex vivo expansion of adult hematopoietic stem cells by overcoming CUL4-mediated degradation of HOXB4. Blood. 2013 May 16;121(20):4082-9
Recommended Validation Protocols: HSC 4-day proliferation
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The role of HoxB4 is well established:
•Constitutive HOXB4 in BMCs increases CFU-GEMM (myeloid) by 1000X at 8 days [1]
•HOXB4 temporary overexpression in donor murine HSCs (LSK) resulted in superior (~3X) reconstitution of myeloid, T-cells and B-cells across murine blood, marrow, and spleen at 6 months after lethal irradiation [2]
•HOXB4 expressing murine HSCs expanded 40X in vitro at 2 weeks, and outcompeted control HSCs, formed all lineages, and caused no myeloproliferative disorders at 9 months after HSC Transplant (HSCT) [3]
•HOXB4 expression confers 16X competitive engraftment advantage on human cord blood HSCs (7 days) into sublethally-irradiated NSG mice at 8 weeks post infusion [4]
•Embryonic Stem Cells exposed to a 1-6 day pulse of HoxB4 (inducible) generate ~5X more hematopoietic colonies of all types, longer exposure increases effect [5]
•Recombinant TAT-HOXB4 expanded CD34+ umbilical cord and peripheral blood HSCs ex vivo (3-6X proliferation, 8-15X CFC in 4 days) and improved primary and secondary HSCT reconstitution [6]
•Recombinant TAT-HOXB4 restored expansion in HSCs from myelodysplastic patients [7]