{"doi":"10.1101/2023.02.09.527726","title":"Single cell transcriptomics identifies adipose tissue CD271+ progenitors for enhanced angiogenesis in limb ischemia","abstract":"SUMMARY Therapeutic angiogenesis using mesenchymal stem/stromal cell grafts have shown modest and controversial effects in preventing amputation for patients with critical limb ischemia. Through single-cell transcriptomic analysis of human tissues, we identified CD271 + progenitors specifically from subcutaneous adipose tissue (AT) as having the most prominent pro-angiogenic gene profile distinct from other stem cell populations. AT-CD271 + progenitors demonstrated robust in vivo angiogenic capacity, over conventional adipose stromal cell grafts, characterized by long-term engraftment, augmented tissue regeneration, and significant recovery of blood flow in a xenograft model of limb ischemia. Mechanistically, the angiogenic capacity of CD271 + progenitors is dependent on functional CD271 and mTOR signaling. Notably, the number and angiogenic capacity of CD271 + progenitors was strikingly reduced in insulin resistant donors. Our study highlights the identification of AT-CD271 + progenitors with in vivo superior efficacy for limb ischemia. Furthermore, we showcase comprehensive single-cell transcriptomics strategies for identification of suitable grafts for cell therapy. HIGHLIGHTS Adipose tissue stromal cells have a distinct angiogenic gene profile among human cell sources. CD271 + progenitors in adipose tissue have a prominent angiogenic gene profile. CD271 + progenitors show superior therapeutic capacities for limb ischemia. CD271 + progenitors are reduced and functionally impaired in insulin resistant donors. GRAPHICAL ABSTRACT","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":398459,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9391,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1139063,"name":"Chiaki Goten","orcid":"0000-0002-8123-7610","position":1,"is_corresponding":false},{"id":1139064,"name":"Daiki Hashimuko","orcid":"0000-0002-0270-3725","position":2,"is_corresponding":false},{"id":1174659,"name":"K Yamaguchi","orcid":"0000-0002-4412-3200","position":3,"is_corresponding":false},{"id":1139066,"name":"Yusuke Takeda","orcid":"0000-0001-5028-1056","position":4,"is_corresponding":false},{"id":1139517,"name":"Ayano Nomura","orcid":null,"position":5,"is_corresponding":false},{"id":1139067,"name":"Hiroshi Ootsuji","orcid":"0000-0003-1290-1351","position":6,"is_corresponding":false},{"id":1139068,"name":"Shinichiro Takashima","orcid":"0000-0002-2071-556X","position":7,"is_corresponding":false},{"id":1139069,"name":"Kenji Iino","orcid":"0000-0002-0051-1092","position":8,"is_corresponding":false},{"id":1139070,"name":"Hirofumi Takemura","orcid":"0000-0001-9188-7820","position":9,"is_corresponding":false},{"id":1139071,"name":"Manasi Halurkar","orcid":"0000-0003-0936-6925","position":10,"is_corresponding":false},{"id":311280,"name":"Hee‐Woong Lim","orcid":"0000-0001-8599-1808","position":11,"is_corresponding":false},{"id":484660,"name":"Vivian Hwa","orcid":"0000-0003-0517-9049","position":12,"is_corresponding":false},{"id":281145,"name":"Joan Sánchez-Gurmaches","orcid":"0000-0003-1854-7832","position":13,"is_corresponding":false},{"id":1139072,"name":"Soichiro Usui","orcid":"0000-0003-1752-8082","position":14,"is_corresponding":false},{"id":408535,"name":"Masayuki Takamura","orcid":"0000-0002-1540-4417","position":15,"is_corresponding":false},{"id":1139062,"name":"Oto Inoue","orcid":"0000-0002-5559-8981","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:19:47.744358Z","pmid":"36865239","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":[]}