{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:30:42Z","timestamp":1788269442594,"version":"build-2803163510"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":58,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LTGY23H080002"],"award-info":[{"award-number":["LTGY23H080002"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82270157"],"award-info":[{"award-number":["82270157"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100022963","name":"Key Research and Development Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2022C03005"],"award-info":[{"award-number":["2022C03005"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Science and Technology of Zhejiang Provinc","award":["2023R01012"],"award-info":[{"award-number":["2023R01012"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"DOI":"10.1186\/s13287-026-05047-9","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:35:29Z","timestamp":1777696529000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Generation and single-cell characterization of functional megakaryocytes derived from umbilical cord blood"],"prefix":"10.1186","volume":"17","author":[{"given":"Yanmin","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faming","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"5047_CR1","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1182\/blood-2017-11-742684","volume":"131","author":"K McArthur","year":"2018","unstructured":"McArthur K, Chappaz S, Kile BT. Apoptosis in megakaryocytes and platelets: the life and death of a lineage. Blood. 2018;131:605\u201310.","journal-title":"Blood"},{"key":"5047_CR2","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.stem.2020.11.006","volume":"28","author":"H Wang","year":"2021","unstructured":"Wang H, He J, Xu C, Chen X, Yang H, Shi S, et al. Decoding human megakaryocyte development. Cell Stem Cell. 2021;28:535\u201349.","journal-title":"Cell Stem Cell"},{"key":"5047_CR3","doi-asserted-by":"publisher","first-page":"e606","DOI":"10.1016\/S2352-3026(19)30200-5","volume":"6","author":"N Roberts","year":"2019","unstructured":"Roberts N, James S, Delaney M, Fitzmaurice C. The global need and availability of blood products: a modelling study. Lancet Haematol. 2019;6:e606\u201315.","journal-title":"Lancet Haematol"},{"issue":"6","key":"5047_CR4","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1080\/09537104.2020.1769051","volume":"31","author":"S Mookerjee","year":"2020","unstructured":"Mookerjee S, Foster HR, Waller AK, Ghevaert CJ. In vitro-derived platelets: the challenges we will have to face to assess quality and safety. Platelets. 2020;31(6):724\u201330.","journal-title":"Platelets"},{"key":"5047_CR5","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1182\/blood.V85.2.402.402","volume":"85","author":"ES Choi","year":"1995","unstructured":"Choi ES, Nichol JL, Hokom MM, Hornkohl AC, Hunt P. Platelets generated in vitro from proplatelet-displaying human megakaryocytes are functional. Blood. 1995;85:402\u201313.","journal-title":"Blood"},{"key":"5047_CR6","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1046\/j.1365-2141.2000.01854.x","volume":"108","author":"R Miyazaki","year":"2000","unstructured":"Miyazaki R, Ogata H, Iguchi T, Sogo S, Kushida T, Ito T, et al. Comparative analyses of megakaryocytes derived from cord blood and bone marrow. Br J Haematol. 2000;108:602\u20139.","journal-title":"Br J Haematol"},{"key":"5047_CR7","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.stem.2014.01.011","volume":"14","author":"S Nakamura","year":"2014","unstructured":"Nakamura S, Takayama N, Hirata S, Seo H, Endo H, Ochi K, et al. Expandable megakaryocyte cell lines enable clinically applicable generation of platelets from human induced pluripotent stem cells. Cell Stem Cell. 2014;14:535\u201348.","journal-title":"Cell Stem Cell"},{"key":"5047_CR8","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1159\/000477261","volume":"44","author":"A Baigger","year":"2017","unstructured":"Baigger A, Blasczyk R, Figueiredo C. Towards the manufacture of megakaryocytes and platelets for clinical application. Transfus Med Hemother. 2017;44:165\u201373.","journal-title":"Transfus Med Hemother"},{"key":"5047_CR9","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.1182\/blood-2014-08-595561","volume":"125","author":"CA Di Buduo","year":"2015","unstructured":"Di Buduo CA, Wray LS, Tozzi L, Malara A, Chen Y, Ghezzi CE, et al. Programmable 3D silk bone marrow niche for platelet generation ex vivo and modeling of megakaryopoiesis pathologies. Blood. 2015;125:2254\u201364.","journal-title":"Blood"},{"key":"5047_CR10","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1111\/jth.13736","volume":"15","author":"N Sugimoto","year":"2017","unstructured":"Sugimoto N, Eto K. Platelet production from induced pluripotent stem cells. J Thromb Haemost. 2017;15:1717\u201327.","journal-title":"J Thromb Haemost"},{"key":"5047_CR11","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.biomaterials.2018.08.019","volume":"182","author":"JH Shepherd","year":"2018","unstructured":"Shepherd JH, Howard D, Waller AK, Foster HR, Mueller A, Moreau T, et al. Structurally graduated collagen scaffolds applied to the ex vivo generation of platelets from human pluripotent stem cell-derived megakaryocytes: enhancing production and purity. Biomaterials. 2018;182:135\u201344.","journal-title":"Biomaterials"},{"issue":"3","key":"5047_CR12","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.cell.2018.06.011","volume":"174","author":"Y Ito","year":"2018","unstructured":"Ito Y, Nakamura S, Sugimoto N, Shigemori T, Kato Y, Ohno M, et al. Turbulence activates platelet biogenesis to enable clinical scale ex\u00a0vivo production. Cell. 2018;174(3):636\u201348.","journal-title":"Cell"},{"issue":"1","key":"5047_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28459-x","volume":"8","author":"D Eicke","year":"2018","unstructured":"Eicke D, Baigger A, Schulze K, Latham SL, Halloin C, Zweigerdt R, et al. Large-scale production of megakaryocytes in microcarrier-supported stirred suspension bioreactors. Sci Rep. 2018;8(1):10146.","journal-title":"Sci Rep"},{"key":"5047_CR14","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1111\/cts.12788","volume":"13","author":"X Guan","year":"2020","unstructured":"Guan X, Wang L, Wang H, Wang H, Dai W, Jiang Y. Good manufacturing practice-grade of megakaryocytes produced by a novel ex vivo culturing platform. Clin Transl Sci. 2020;13:1115\u201326.","journal-title":"Clin Transl Sci"},{"key":"5047_CR15","doi-asserted-by":"publisher","first-page":"E9308","DOI":"10.1073\/pnas.1805434115","volume":"115","author":"F Zhu","year":"2018","unstructured":"Zhu F, Feng M, Sinha R, Seita J, Mori Y, Weissman IL. Screening for genes that regulate the differentiation of human megakaryocytic lineage cells. Proc Natl Acad Sci U S A. 2018;115:E9308\u201316.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"5047_CR16","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/978-1-4939-8585-2_10","volume":"1812","author":"T Moreau","year":"2018","unstructured":"Moreau T, Evans AL, Ghevaert CJG. Differentiation of human pluripotent stem cells to megakaryocytes by transcription factor-driven forward programming. Methods Mol Biol. 2018;1812:155\u201376.","journal-title":"Methods Mol Biol"},{"key":"5047_CR17","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1016\/j.stemcr.2018.11.001","volume":"11","author":"A Dalby","year":"2018","unstructured":"Dalby A, Ballester-Beltr\u00e1n J, Lincetto C, Mueller A, Foad N, Evans A, et al. Transcription factor levels after forward programming of human pluripotent stem cells with GATA1, FLI1, and TAL1 determine megakaryocyte versus erythroid cell fate decision. Stem Cell Rep. 2018;11:1462\u201378.","journal-title":"Stem Cell Rep"},{"key":"5047_CR18","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.stemcr.2017.12.017","volume":"10","author":"H Wang","year":"2018","unstructured":"Wang H, Liu C, Liu X, Wang M, Wu D, Gao J, et al. MEIS1 regulates hemogenic endothelial generation, megakaryopoiesis, and thrombopoiesis in human pluripotent stem cells by targeting TAL1 and FLI1. Stem Cell Rep. 2018;10:447\u201360.","journal-title":"Stem Cell Rep"},{"key":"5047_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.transci.2022.103481","volume":"61","author":"Z Mansoorabadi","year":"2022","unstructured":"Mansoorabadi Z, Kheirandish M. The upregulation of Gata transcription factors family and FOG-1 in expanded and differentiated cord blood-derived CD34+\u00a0hematopoietic stem cells to megakaryocyte lineage during co-culture with cord blood mesenchymal stem cells. Transfus Apher Sci. 2022;61:103481.","journal-title":"Transfus Apher Sci"},{"key":"5047_CR20","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.stemcr.2014.09.010","volume":"3","author":"Q Feng","year":"2014","unstructured":"Feng Q, Shabrani N, Thon JN, Huo H, Thiel A, Machlus KR, et al. Scalable generation of universal platelets from human induced pluripotent stem cells. Stem Cell Rep. 2014;3:817\u201331.","journal-title":"Stem Cell Rep"},{"key":"5047_CR21","doi-asserted-by":"publisher","first-page":"11208","DOI":"10.1038\/ncomms11208","volume":"7","author":"T Moreau","year":"2016","unstructured":"Moreau T, Evans AL, Vasquez L, Tijssen MR, Yan Y, Trotter MW, et al. Large scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming. Nat Commun. 2016;7:11208.","journal-title":"Nat Commun"},{"key":"5047_CR22","doi-asserted-by":"publisher","first-page":"274","DOI":"10.2119\/molmed.2015.00235","volume":"22","author":"AK B\u00f6rger","year":"2016","unstructured":"B\u00f6rger AK, Eicke D, Wolf C, Gras C, Aufderbeck S, Schulze K, et al. Generation of HLA-universal iPSC-derived megakaryocytes and platelets for survival under refractoriness conditions. Mol Med. 2016;22:274\u201385.","journal-title":"Mol Med"},{"key":"5047_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-65577-x","volume":"10","author":"P Norbnop","year":"2020","unstructured":"Norbnop P, Ingrungruanglert P, Israsena N, Suphapeetiporn K, Shotelersuk V. Generation and characterization of HLA-universal platelets derived from induced pluripotent stem cells. Sci Rep. 2020;10:8472.","journal-title":"Sci Rep"},{"key":"5047_CR24","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/s41580-021-00335-z","volume":"22","author":"H Wang","year":"2021","unstructured":"Wang H, Yang Y, Liu J, Qian L. Direct cell reprogramming: approaches, mechanisms and progress. Nat Rev Mol Cell Biol. 2021;22:410\u201324.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"5047_CR25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1018047","volume":"13","author":"B Kumar","year":"2022","unstructured":"Kumar B, Afshar-Kharghan V, Mendt M, Sackstein R, Tanner MR, Popat U, et al. Engineered cord blood megakaryocytes evade killing by allogeneic T-cells for refractory thrombocytopenia. Front Immunol. 2022;13:1018047.","journal-title":"Front Immunol"},{"key":"5047_CR26","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1016\/j.stem.2022.07.004","volume":"29","author":"J Qin","year":"2022","unstructured":"Qin J, Zhang J, Jiang J, Zhang B, Li J, Lin X, et al. Direct chemical reprogramming of human cord blood erythroblasts to induced megakaryocytes that produce platelets. Cell Stem Cell. 2022;29:1229\u201345.","journal-title":"Cell Stem Cell"},{"key":"5047_CR27","first-page":"1","volume":"130","author":"J Perdomo","year":"2017","unstructured":"Perdomo J, Yan F, Leung HHL, Chong BH. Megakaryocyte differentiation and platelet formation from human cord blood-derived CD34+ cells. J Vis Exp. 2017;130:1\u20138.","journal-title":"J Vis Exp"},{"key":"5047_CR28","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1182\/blood-2018-04-842641","volume":"133","author":"K Tozawa","year":"2019","unstructured":"Tozawa K, Ono-Uruga Y, Yazawa M, Mori T, Murata M, Okamoto S, et al. Megakaryocytes and platelets from a novel human adipose tissue-derived mesenchymal stem cell line. Blood. 2019;133:633\u201343.","journal-title":"Blood"},{"key":"5047_CR29","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.stemcr.2019.11.011","volume":"14","author":"D Suzuki","year":"2020","unstructured":"Suzuki D, Flahou C, Yoshikawa N, Stirblyte I, Hayashi Y, Sawaguchi A, et al. iPSC-derived platelets depleted of HLA class I are inert to anti-HLA class I and natural killer cell immunity. Stem Cell Reports. 2020;14:49\u201359.","journal-title":"Stem Cell Reports"},{"issue":"14","key":"5047_CR30","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1182\/blood.2021010697","volume":"138","author":"S Sun","year":"2021","unstructured":"Sun S, Jin C, Si J, Lei Y, Chen K, Cui Y, et al. Single-cell analysis of ploidy and the transcriptome reveals functional and spatial divergency in murine megakaryopoiesis. Blood. 2021;138(14):1211\u201324.","journal-title":"Blood"},{"key":"5047_CR31","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1038\/s41417-022-00476-z","volume":"29","author":"W Zhang","year":"2022","unstructured":"Zhang W, Yan C, Liu X, Yang P, Wang J, Chen Y, et al. Global characterization of megakaryocytes in bone marrow, peripheral blood, and cord blood by single-cell RNA sequencing. Cancer Gene Ther. 2022;29:1636\u201347.","journal-title":"Cancer Gene Ther"},{"key":"5047_CR32","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","volume":"42","author":"Y Hao","year":"2024","unstructured":"Hao Y, Stuart T, Kowalski MH, Choudhary S, Hoffman P, Hartman A, et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat Biotechnol. 2024;42:293\u2013304.","journal-title":"Nat Biotechnol"},{"key":"5047_CR33","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-018-4772-0","volume":"19","author":"K Street","year":"2018","unstructured":"Street K, Risso D, Fletcher RB, Das D, Ngai J, Yosef N, et al. Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics. 2018;19:477.","journal-title":"BMC Genomics"},{"key":"5047_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2022.101266","volume":"3","author":"G Wang","year":"2022","unstructured":"Wang G, Wen WX, Mead AJ, Roy A, Psaila B, Thongjuea S. Processing single-cell RNA-seq datasets using SingCellaR. STAR Protoc. 2022;3:101266.","journal-title":"STAR Protoc"},{"key":"5047_CR35","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1080\/09537104.2021.1936479","volume":"33","author":"S Tan","year":"2022","unstructured":"Tan S, Zhang J, Sun Y, Gister\u00e5 A, Sheng Z, Malmstr\u00f6m RE, et al. Platelets enhance CD4+ central memory T cell responses via platelet factor 4-dependent mitochondrial biogenesis and cell proliferation. Platelets. 2022;33:360\u201370.","journal-title":"Platelets"},{"key":"5047_CR36","doi-asserted-by":"publisher","first-page":"1098665","DOI":"10.3389\/fimmu.2023.1098665","volume":"14","author":"ZY Liu","year":"2023","unstructured":"Liu ZY, Sun MX, Hua MQ, Zhang HX, Mu GY, Zhou S, et al. New perspectives on the induction and acceleration of immune-associated thrombosis by PF4 and VWF. Front Immunol. 2023;14:1098665.","journal-title":"Front Immunol"},{"key":"5047_CR37","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1182\/blood.2023020872","volume":"143","author":"RJ Buka","year":"2024","unstructured":"Buka RJ, Montague SJ, Moran LA, Martin EM, Slater A, Watson SP, et al. PF4 activates the c-Mpl-Jak2 pathway in platelets. Blood. 2024;143:64\u20139.","journal-title":"Blood"},{"key":"5047_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2023.101155","volume":"64","author":"Z Liu","year":"2024","unstructured":"Liu Z, Li L, Zhang H, Pang X, Qiu Z, Xiang Q, et al. Platelet factor 4(PF4) and its multiple roles in diseases. Blood Rev. 2024;64:101155.","journal-title":"Blood Rev"},{"key":"5047_CR39","doi-asserted-by":"publisher","first-page":"5199","DOI":"10.1182\/blood-2006-11-059378","volume":"109","author":"AG Muntean","year":"2007","unstructured":"Muntean AG, Pang L, Poncz M, Dowdy SF, Blobel GA, Crispino JD. Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization. Blood. 2007;109:5199\u2013207.","journal-title":"Blood"},{"key":"5047_CR40","first-page":"3328","volume":"10","author":"Y Huang","year":"2020","unstructured":"Huang Y, Lin L, Shen Z, Li Y, Cao H, Peng L, et al. CEBPG promotes esophageal squamous cell carcinoma progression by enhancing PI3K-AKT signaling. Am J Cancer Res. 2020;10:3328\u201344.","journal-title":"Am J Cancer Res"}],"container-title":["Stem Cell Research & Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-026-05047-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-026-05047-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-026-05047-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T06:59:11Z","timestamp":1782716351000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13287-026-05047-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,2]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5047"],"URL":"https:\/\/doi.org\/10.1186\/s13287-026-05047-9","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,2]]},"assertion":[{"value":"10 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the UCB samples were collected and used under the approval of the Ethical Committee of the Blood Center of Zhejiang Province. Title of the project is \"Bioengineered iPSC-derived megakaryocytes for the detection of HPA-15 specific alloantibodies\" and the date of approval is February 3rd, 2023. Written informed consents were obtained from all the donors for the use of their samples in this study. The animal experiments were approved by the Institutional Animal Care and Use Committee, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University and title of the protocol is \"In vivo functional assessment of HLA universal megakaryocytes\" (Approved date: September 9th, 2024).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"227"}}