biostudies-literatureChen YScience and Technology Commission of Shanghai MunicipalityNational Natural Science Foundation of ChinaMajor Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration ZoneNational Key Research and Development Program of China11https://www.ebi.ac.uk/biostudies/studies/S-EPMC9872349biostudies-literatureUnknown14(1)Hypoimmunogenic human pluripotent stem cells (hPSCs) are expected to serve as an unlimited cell source for generating universally compatible "off-the-shelf" cell grafts. However, whether the engineered hypoimmunogenic hPSCs still preserve their advantages of unlimited self-renewal and multilineage differentiation to yield functional tissue cells remains unclear. Here, we systematically studied the self-renewal and differentiation potency of three types of hypoimmunogenic hPSCs, established through the biallelic lesion of B2M gene to remove all surface expression of classical and nonclassical HLA class I molecules (B2M^null), biallelic homologous recombination of nonclassical HLA-G1 to the B2M loci to knockout B2M while expressing membrane-bound β2m-HLA-G1 fusion proteins (B2M<supStem cell research & therapyHypoimmunogenic human pluripotent stem cells are valid cell sources for cell therapeutics with normal self-renewal and multilineage differentiation capacity.PMC9872349320006892021YFC27014002018YFA010800019JC1415100822300723187276032270874ZJ2018-ZD-0042021YFA1100400211409023002019YFA011030082025020Fang YXiong JMa LLiu LZhang XChen YZhou YZhou ZfalseHypoimmunogenic human pluripotent stem cells are valid cell sources for cell therapeutics with normal self-renewal and multilineage differentiation capacity.Hypoimmunogenic human pluripotent stem cells (hPSCs) are expected to serve as an unlimited cell source for generating universally compatible "off-the-shelf" cell grafts. However, whether the engineered hypoimmunogenic hPSCs still preserve their advantages of unlimited self-renewal and multilineage differentiation to yield functional tissue cells remains unclear. Here, we systematically studied the self-renewal and differentiation potency of three types of hypoimmunogenic hPSCs, established through the biallelic lesion of B2M gene to remove all surface expression of classical and nonclassical HLA class I molecules (B2M^null), biallelic homologous recombination of nonclassical HLA-G1 to the B2M loci to knockout B2M while expressing membrane-bound β2m-HLA-G1 fusion proteins (B2M<sup2023-01-01T00:00:00Z2023 Jan2025-04-04T13:08:04.015Z2025-04-04T13:08:04.015ZS-EPMC98723493669108610.1186/s13287-022-03233-z