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To investigate the molecular basis of this resistance, we applied single-cell RNA sequencing to coisogenic parasite lines, K13 wild-type (K13\n                  <jats:sup>C580<\/jats:sup>\n                  ) and the artemisinin-resistant mutant (K13\n                  <jats:sup>580Y<\/jats:sup>\n                  ), following a 6 hour pulse of dihydroartemisinin (DHA). This approach enabled high-resolution profiling across intraerythrocytic stages. Both lines exhibited stage-specific transcriptional responses, with pronounced changes in ring and trophozoite stages. Using Manifold Enhancement of Latent Dimensions (MELD), a computational framework for quantifying transcriptional perturbation, DHA-treatment induces stage-specific differences in protein export and metabolic pathways in K13\n                  <jats:sup>C580<\/jats:sup>\n                  and K13\n                  <jats:sup>580Y<\/jats:sup>\n                  parasites, relating to an altered metabolic stress response state. GARP, a potential therapeutic target, was highly differentially expressed in untreated ring stages of K13\n                  <jats:sup>580Y<\/jats:sup>\n                  and K13\n                  <jats:sup>C580<\/jats:sup>\n                  . Functional assays confirmed that anti-GARP antibodies retained efficacy against K13\n                  <jats:sup>580Y<\/jats:sup>\n                  , supporting its potential as a therapeutic target. These findings provide a comprehensive view of the cellular responses related to artemisinin resistance, identify molecular features of pathogenesis, and highlight surface proteins like GARP as promising intervention targets. This work underscores the power of single-cell approaches to dissect drug responses and guide strategies to overcome resistant parasites.\n                <\/jats:p>","DOI":"10.1101\/2023.12.06.570387","type":"posted-content","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T22:25:21Z","timestamp":1701901521000},"source":"Crossref","is-referenced-by-count":0,"title":["Single-cell transcriptional changes of artemisinin-sensitive K13\n                  <sup>C580<\/sup>\n                  and artemisinin-resistant K13\n                  <sup>580Y<\/sup>\n                  <i>Plasmodium falciparum<\/i>\n                  upon dihydroartemisinin exposure"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7330-7340","authenticated-orcid":false,"given":"Sean V.","family":"Connelly","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clark","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Petrow","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA"},{"name":"Center for International Health Research, Providence, RI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazrin","family":"Rustamzade","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Zuromski","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah M.","family":"Sipolski","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9243-5567","authenticated-orcid":false,"given":"Christian P.","family":"Nixon","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1032-9558","authenticated-orcid":false,"given":"Jonathan D.","family":"Kurtis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA"},{"name":"Center for International Health Research, Providence, RI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0591-0850","authenticated-orcid":false,"given":"Jonathan J.","family":"Juliano","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA"},{"name":"Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA"},{"name":"Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA"},{"name":"Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6899-8204","authenticated-orcid":false,"given":"Jeffrey A.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6914-4032","authenticated-orcid":false,"given":"Cliff I.","family":"Oduor","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026022609000781000_2023.12.06.570387v4.1","unstructured":"World Health Organization. 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