{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:29:01Z","timestamp":1791862141393,"version":"4.3.4"},"reference-count":61,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T00:00:00Z","timestamp":1628380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0112402"],"award-info":[{"award-number":["2020YFA0112402"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFA0100601"],"award-info":[{"award-number":["2016YFA0100601"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFA0103401"],"award-info":[{"award-number":["2017YFA0103401"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770152"],"award-info":[{"award-number":["81770152"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070152"],"award-info":[{"award-number":["82070152"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81890991"],"award-info":[{"award-number":["81890991"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31871173"],"award-info":[{"award-number":["31871173"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900115"],"award-info":[{"award-number":["81900115"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900110"],"award-info":[{"award-number":["81900110"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M663399"],"award-info":[{"award-number":["2019M663399"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Characterization of functional T\u00a0cell clusters is key to developing strategies for immunotherapy and predicting clinical responses in leukemia. Here, single\u2010cell RNA sequencing is performed with T\u00a0cells sorted from the peripheral blood of healthy individuals and patients with B cell\u2010acute lymphoblastic leukemia (B\u2010ALL). Unbiased bioinformatics analysis enabled the authors to identify 13 T\u00a0cell clusters in the patients based on their molecular properties. All 11 major T\u00a0cell subsets in healthy individuals are found in the patients with B\u2010ALL, with the counterparts in the patients universally showing more activated characteristics. Two exhausted T\u00a0cell populations, characterized by up\u2010regulation of\n                    <jats:italic>TIGIT<\/jats:italic>\n                    ,\n                    <jats:italic>PDCD1<\/jats:italic>\n                    ,\n                    <jats:italic>HLADRA<\/jats:italic>\n                    ,\n                    <jats:italic>LAG3<\/jats:italic>\n                    , and\n                    <jats:italic>CTLA4<\/jats:italic>\n                    are specifically discovered in B\u2010ALL patients. Of note, these exhausted T\u00a0cells possess remarkable heterogeneity, and ten sub\u2010clusters are further identified, which are characterized by different cell cycle phases, na\u00efve states, and\n                    <jats:italic>GNLY<\/jats:italic>\n                    (coding granulysin) expression. Coupled with single\u2010cell T\u00a0cell receptor repertoire profiling, diverse originations of the exhausted T\u00a0cells in B\u2010ALL are suggested, and clonally expanded exhausted T\u00a0cells are likely to originate from CD8\n                    <jats:sup>+<\/jats:sup>\n                    effector memory\/terminal effector cells. Together, these data provide for the first\u2010time valuable insights for understanding exhausted T\u00a0cell populations in leukemia.\n                  <\/jats:p>","DOI":"10.1002\/advs.202101447","type":"journal-article","created":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T09:06:38Z","timestamp":1628413598000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Single\u2010Cell RNA\u2010Seq of T Cells in B\u2010ALL Patients Reveals an Exhausted Subset with Remarkable Heterogeneity"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1601-7814","authenticated-orcid":false,"given":"Xiaofang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Hematology First Affiliated Hospital Jinan University  No. 601 West of Huangpu Avenue Guangzhou 510632 China"},{"name":"Key Laboratory for Regenerative Medicine of Ministry of Education Institute of Hematology School of Medicine Jinan University  Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9371-0313","authenticated-orcid":false,"given":"Yanjuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory for Regenerative Medicine of Ministry of Education Institute of Hematology School of Medicine Jinan University  Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5189-5268","authenticated-orcid":false,"given":"Zongcheng","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology Institute of Hematology Fifth Medical Center of Chinese PLA General Hospital  Beijing 100071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyan","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Regenerative Medicine of Ministry of Education Institute of Hematology School of Medicine Jinan University  Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7044-7663","authenticated-orcid":false,"given":"Ling","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Hematology First Affiliated Hospital Jinan University  No. 601 West of Huangpu Avenue Guangzhou 510632 China"},{"name":"Key Laboratory for Regenerative Medicine of Ministry of Education Institute of Hematology School of Medicine Jinan University  Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Hematology First Affiliated Hospital Jinan University  No. 601 West of Huangpu Avenue Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9017-2185","authenticated-orcid":false,"given":"Yuhong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Hematology First Affiliated Hospital Jinan University  No. 601 West of Huangpu Avenue Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4970-1305","authenticated-orcid":false,"given":"Xianfeng","family":"Zha","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory First Affiliated Hospital School of Medicine Jinan University  No. 601 West of Huangpu Avenue Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7313-6924","authenticated-orcid":false,"given":"Bing","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology Institute of Hematology Fifth Medical Center of Chinese PLA General Hospital  Beijing 100071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4731-5945","authenticated-orcid":false,"given":"Yu","family":"Lan","sequence":"additional","affiliation":[{"name":"Key Laboratory for Regenerative Medicine of Ministry of Education Institute of Hematology School of Medicine Jinan University  Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0974-4036","authenticated-orcid":false,"given":"Yangqiu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology First Affiliated Hospital Jinan University  No. 601 West of Huangpu Avenue Guangzhou 510632 China"},{"name":"Key Laboratory for Regenerative Medicine of Ministry of Education Institute of Hematology School of Medicine Jinan University  Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,8]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05690"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.03.012"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06866"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar4060"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.12.002"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407222"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21349"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.02.048"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2008.09.003"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.03.001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.11.043"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.060"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.035"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0734-6"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2019.07.009"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0276-y"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2297"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1600674113"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh320"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0569"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3405"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0501"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.017"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.04.015"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2015.12.006"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2015.1056953"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2938"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0078-7"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1895-7"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.21147\/j.issn.1000-9604.2019.02.15"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.76"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.12.001"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2282"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04334-1"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019001181"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0096-5"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.07.011"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13071536"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-018-0814-0"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0694-x"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.031"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0045-3"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19330"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3800"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2005.04.011"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1916206117"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2020.11.008"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1382-0"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.002"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0501"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-632"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.094243"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11247"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.01.004"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1603-1"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa611"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202101447","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202101447","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202101447","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T15:12:02Z","timestamp":1759763522000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202101447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,8]]},"references-count":61,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/advs.202101447"],"URL":"https:\/\/doi.org\/10.1002\/advs.202101447","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,8]]},"assertion":[{"value":"2021-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2101447"}}