In addition, given the loss of RB1 function in the genetically engineered hESCs at the beginning of differentiation, all cells in the Rb organoids derived from these hESCs will lose RB1 function, which will also lead to significant decrease of normal retinal cells in this model system, which may be not suitable for studying tumor microenvironment, invasion or metastasis. The gene discussed is RB1; the disease is neoplasm.