{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:46:20Z","timestamp":1747183580392,"version":"3.40.5"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T00:00:00Z","timestamp":1571011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["106\u20102314\u2010B\u2010182\u2010059\u2010MY3","108\u20102314\u2010B\u2010182\u2010045\u2010MY3"],"award-info":[{"award-number":["106\u20102314\u2010B\u2010182\u2010059\u2010MY3","108\u20102314\u2010B\u2010182\u2010045\u2010MY3"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Significant phenotypic heterogeneity exists in patients with all subtypes of myeloproliferative neoplasms (MPN), including essential thrombocythaemia (ET). Single\u2010cell RNA sequencing (scRNA\u2010Seq) holds the promise of unravelling the biology of MPN at an unprecedented level of resolution. Herein we employed this approach to dissect the transcriptomes in the CD34<jats:sup>+<\/jats:sup> cells from the peripheral blood of seven previously untreated ET patients and one healthy adult. The mutational profiles in these patients were as follows: <jats:italic>JAK2<\/jats:italic> V617F in two, <jats:italic>CALR<\/jats:italic> in three (one type I and two type II) and triple\u2010negative (TN) in two. Our results reveal substantial heterogeneity within this enrolled cohort of patients. Activation of JAK\/STAT signalling was recognized in discrepant progenitor lineages among different samples. Significantly disparate molecular profiling was identified in the comparison between ET patients and the control, between patients with different driver mutations <jats:bold><jats:italic>(<\/jats:italic><\/jats:bold><jats:italic>JAK2<\/jats:italic> V617F and <jats:italic>CALR<\/jats:italic> exon 9 indel), and even between patients harbouring the same driver. Intra\u2010individual clonal diversity was also found in the CD34<jats:sup>+<\/jats:sup> progenitor population of a patient, possibly indicating the presence of multiple clones in this case. Estimation of subpopulation size based on cellular immunophenotyping suggested differentiation bias in all analysed samples. Furthermore, combining the transcriptomic information with data from targeted sequencing enabled us to unravel key somatic mutations that are molecularly relevant. To conclude, we demonstrated that scRNA\u2010Seq extended our knowledge of clonal diversity and inter\u2010individual heterogeneity in patients with ET. The obtained information could potentially leapfrog our efforts in the elucidation of the pathogenesis of the disease.<\/jats:p>","DOI":"10.1111\/bjh.16225","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T23:55:20Z","timestamp":1571097320000},"page":"707-722","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Molecular heterogeneity unravelled by single\u2010cell transcriptomics in patients with essential thrombocythaemia"],"prefix":"10.1111","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6138-8262","authenticated-orcid":false,"given":"Chia\u2010Chen","family":"Hsu","sequence":"first","affiliation":[{"name":"Division of Haematology and Oncology Department of Medicine Chang Gung Memorial Hospital Chiayi Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying\u2010Ju","family":"Chen","sequence":"additional","affiliation":[{"name":"Division 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