{"doi":"10.12688/wellcomeopenres.18034.1","title":"Tumor suppressors inhibit reprogramming of African spiny mouse (Acomys) fibroblasts to induced pluripotent stem cells","abstract":"<ns4:p> <ns4:bold>Background:</ns4:bold> The African spiny mouse ( <ns4:italic>Acomys</ns4:italic> ) is an emerging mammalian model for scar-free regeneration, and further study of <ns4:italic>Acomys</ns4:italic> could advance the field of regenerative medicine. Isolation of pluripotent stem cells from <ns4:italic>Acomys</ns4:italic> would allow for development of transgenic or chimeric animals and <ns4:italic>in vitro</ns4:italic> study of regeneration; however, the reproductive biology of <ns4:italic>Acomys</ns4:italic> is not well characterized, complicating efforts to derive embryonic stem cells. Thus, we sought to generate <ns4:italic>Acomys</ns4:italic> induced pluripotent stem cells (iPSCs) by reprogramming somatic cells back to pluripotency. </ns4:p> <ns4:p> <ns4:bold>Methods:</ns4:bold> To generate <ns4:italic>Acomys</ns4:italic> iPSCs, we attempted to adapt established protocols developed in <ns4:italic>Mus</ns4:italic> . We utilized a PiggyBac transposon system to genetically modify <ns4:italic>Acomys</ns4:italic> fibroblasts to overexpress the Yamanaka reprogramming factors as well as mOrange fluorescent protein under the control of a doxycycline-inducible TetON operon system. </ns4:p> <ns4:p> <ns4:bold>Results:</ns4:bold> Reprogramming factor overexpression caused <ns4:italic>Acomys</ns4:italic> fibroblasts to undergo apoptosis or senescence. When SV40 Large T antigen (SV40 LT) was added to the reprogramming cocktail, <ns4:italic>Acomys</ns4:italic> cells were able to dedifferentiate into pre-iPSCs. Although use of 2iL culture conditions induced formation of colonies resembling <ns4:italic>Mus</ns4:italic> PSCs, these <ns4:italic>Acomys</ns4:italic> iPS-like cells lacked pluripotency marker expression and failed to form embryoid bodies. An EOS-GiP system was unsuccessful in selecting for bona fide <ns4:italic>Acomys</ns4:italic> iPSCs; however, inclusion of Nanog in the reprogramming cocktail along with 5-azacytidine in the culture medium allowed for generation of <ns4:italic>Acomys</ns4:italic> iPSC-like cells with increased expression of several naïve pluripotency markers. </ns4:p> <ns4:p> <ns4:bold>Conclusions:</ns4:bold> There are significant roadblocks to reprogramming <ns4:italic>Acomys</ns4:italic> cells, necessitating future studies to determine <ns4:italic>Acomys</ns4:italic> -specific reprogramming factor and/or culture condition requirements. The requirement for SV40 LT during <ns4:italic>Acomys</ns4:italic> dedifferentiation may suggest that tumor suppressor pathways play an important role in <ns4:italic>Acomys</ns4:italic> regeneration and that <ns4:italic>Acomys</ns4:italic> may possess unreported cancer resistance. </ns4:p>","journal":"Wellcome Open Research","year":2022,"id":285294,"datarank":0.3647215453682825,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.09595762498407426,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.09595762498407426,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":4,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":314792,"name":"Malcolm Maden","orcid":"0000-0001-7178-5309","position":1,"is_corresponding":false},{"id":963493,"name":"Lawrence E. Bates","orcid":"0000-0002-2675-309X","position":2,"is_corresponding":false},{"id":562321,"name":"José Silva","orcid":"0000-0001-5487-1117","position":3,"is_corresponding":false},{"id":467918,"name":"Aaron Gabriel W. Sandoval","orcid":"0000-0003-2377-2815","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:29:40.826853Z","pmid":"36060301","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}