{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:29:36Z","timestamp":1790306976854,"version":"4.1.0"},"reference-count":19,"publisher":"IMR Press","issue":"8","license":[{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"973 Project","award":["2013CB531206"],"award-info":[{"award-number":["2013CB531206"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Residual undifferentiated induced pluripotent stem cells (iPSCs) detection is essential for both Embryonic Stem Cells (ESCs) and iPSCs application in final cell therapy products. However, specific differentiated cells require specific genes for residual detection; identifying the suitable marker is costly and time-consuming. Thus, a universal marker for iPSCs residue detection for all three germline cells would greatly benefit PSC-derived cellular therapies. Methods: Next-generation sequencing (NGS) was performed on total RNAs isolated from the iPSC cell lines and embryonic stem cells (H9), the top 30 expressed genes were selected as candidates. By analysis expression fold change comparing iPSC cells to the differentiated cells, seven genes were highly expressed in iPSCs but showed minimal background expression in differentiated cells. Tissue expression pattern of the candidate genes were explored in the Genotype-Tissue Expression (GTEx) project database, candidate genes were narrowed down to two genes. Spike-in experiments were performed to determine the detection limit and correlation with the number of iPSCs and gene expression by ddPCR. Results: By next-generation sequencing (NGS), we identified two marker genes (ESRG and ZSCAN10) suitable for universal undifferentiated iPSC detection. Both ESRG and ZSCAN10 are highly expressed in iPSCs. ZSCAN10 is slightly expressed in the testis, pituitary, and cerebellum; ESRG is highly expressed in the vagina and scarcely expressed in the other tissues. Furthermore, the ddPCR method with a probe and primers for ESRG and ZSCAN10 detected a trace of undifferentiated hiPSCs to a spiked level of 0.0001%. Conclusions: These results suggest that targeting ESRG\/ZSCAN10 transcripts is highly sensitive, quantitative, and could be broadly applied to quality control of almost all iPSC-derived cell therapy products.<\/jats:p>","DOI":"10.31083\/j.fbl2708239","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T01:46:34Z","timestamp":1660268794000},"source":"Crossref","is-referenced-by-count":7,"title":["Universal Markers for hiPSCs Residue Detection"],"prefix":"10.31083","volume":"27","author":[{"given":"Hui","family":"Shi","sequence":"first","affiliation":[{"name":"Molecular Pharmacology Laboratory, Institute of Molecular Medicine, Peking University, 100871 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiejun","family":"Feng","sequence":"first","affiliation":[{"name":"Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, 100176 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"first","affiliation":[{"name":"Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, 100176 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lida","family":"Wu","sequence":"first","affiliation":[{"name":"Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, 100176 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchun","family":"Gu","sequence":"first","affiliation":[{"name":"Molecular Pharmacology Laboratory, Institute of Molecular Medicine, Peking University, 100871 Beijing, China"},{"name":"Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, 100176 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Shi Y, Inoue H, Wu JC, Yamanaka S. Induced pluripotent stem cell technology: a decade of progress. Nature Reviews Drug Discovery. 2017; 16: 115\u2013130.","DOI":"10.1038\/nrd.2016.245"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors. Cell. 2007; 131: 861\u2013872.","DOI":"10.1016\/j.cell.2007.11.019"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Taylor C, Peacock S, Chaudhry A, Bradley JA, Bolton E. Generating an iPSC Bank for HLA-Matched Tissue Transplantation Based on Known Donor and Recipient HLA Types. 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