{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:27:59Z","timestamp":1787574479046,"version":"build-2736575974"},"reference-count":100,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Medicine, Loma Linda University"},{"name":"Loma Linda University GRASP"},{"name":"Loma Linda University Research Innovation","award":["TRDRP-T32FT4859"],"award-info":[{"award-number":["TRDRP-T32FT4859"]}]},{"name":"Loma Linda University Research Innovation","award":["TRDRP-T29IR0437"],"award-info":[{"award-number":["TRDRP-T29IR0437"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Adult hematopoietic stem cells (HSCs) and bone marrow (BM) mesenchymal stem\/stromal cells (MSCs) are essential for lifelong hematopoiesis, skeletal homeostasis, immune competence, and tissue regeneration. The use of electronic cigarettes (E-cigs) among women of reproductive age continues to rise, raising concerns about potential adverse developmental effects; however, the long-term consequences of maternal E-cig vaping on offspring BM stem cell function and hematopoietic homeostasis remain incompletely understood. Here, using a rat model of maternal E-cig exposure (containing nicotine) during gestation, combined with longitudinal in vivo analyses and complementary ex vivo studies of human cells, we show that prenatal E-cig exposure is associated with persistent alterations in offspring BM stem cell function and lineage commitment. Gestational E-cig exposure was associated with expansion of the CD11b\/c+ myeloid-enriched compartment, increased CD90+ stromal cells, and impaired osteogenic differentiation in rat offspring. Complementary experiments using primary human cells showed that nicotine exposure was associated with reduced T-cell proliferation and impaired cytotoxic activity in a proof-of-principle co-culture assay. Mechanistically, transcriptomic profiling followed by Gene Ontology and pathway enrichment analyses identified alterations in molecular programs associated with KLF4\u2013Notch1 signaling, mitochondrial biogenesis, inflammation, and stem cell regulation in the BM of E-cig-exposed rat offspring. Changes in CCL11, FTO, and RUNX2 were additionally associated with an inflammatory and aging-related molecular phenotype that persisted from early life into adulthood, although these findings do not establish a causal CCL11\u2013FTO\u2013RUNX2 signaling axis or direct cellular senescence. Collectively, our study provides a phenotypic and mechanistic framework for understanding how maternal E-cig exposure may influence long-term offspring hematopoietic, skeletal, and immune health while highlighting the need for further studies to establish causal molecular mechanisms and determine their relevance to maternal E-cig use in humans.<\/jats:p>","DOI":"10.3390\/cells15171521","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:47:19Z","timestamp":1787572039000},"page":"1521","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal E-Cigarette Vaping Drives Persistent Reprogramming of Bone Marrow Hematopoietic and Mesenchymal Stem Cells and Promotes Transcriptional and Metabolic Dysregulation-Associated Inflammaging and Disease Risks in Rat Offspring"],"prefix":"10.3390","volume":"15","author":[{"given":"Jeffrey","family":"Xiao","sequence":"first","affiliation":[{"name":"Division of Discovery, Innovation and Regenerative Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Discovery, Innovation and Regenerative Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Lawrence D. Longo MD Center for Perinatal Biology, Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samiksha","family":"Wasnik","sequence":"additional","affiliation":[{"name":"Division of Discovery, Innovation and Regenerative Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzad Daniel","family":"Fattah","sequence":"additional","affiliation":[{"name":"Division of Discovery, Innovation and Regenerative Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Codorniz","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laren","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Saca","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela Lobo","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Matus","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1747-8070","authenticated-orcid":false,"given":"Saied","family":"Mirshahidi","sequence":"additional","affiliation":[{"name":"Biospecimen Laboratory, Department of Medicine and Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"},{"name":"Division of Hematology and Oncology, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"},{"name":"Cancer Center, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7938-4702","authenticated-orcid":false,"given":"Raja R.","family":"Narayan","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, Loma Linda University, Loma Linda, CA 92350, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid M.","family":"Said","sequence":"additional","affiliation":[{"name":"Department of Physiology, Biophysics and Medicine, School of Medicine, University of California, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7911-7118","authenticated-orcid":false,"given":"Hamid","family":"Mirshahidi","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"},{"name":"Cancer Center, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8784-0226","authenticated-orcid":false,"given":"Mark E.","family":"Reeves","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"},{"name":"Cancer Center, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisham","family":"Abdel-Azim","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"},{"name":"Cancer Center, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huynh","family":"Cao","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"},{"name":"Cancer Center, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0063-986X","authenticated-orcid":false,"given":"Subburaman","family":"Mohan","sequence":"additional","affiliation":[{"name":"Musculoskeletal Disease Center, Veterans Affairs Loma Linda Healthcare System, Loma Linda, CA 92357, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Baylink","sequence":"additional","affiliation":[{"name":"Division of Discovery, Innovation and Regenerative Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6917-184X","authenticated-orcid":false,"given":"Yi","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Discovery, Innovation and Regenerative Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"},{"name":"Division of Hematology and Oncology, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"},{"name":"Cancer Center, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41562-021-01202-9","article-title":"Earliest evidence for human use of tobacco in the Pleistocene Americas","volume":"6","author":"Duke","year":"2022","journal-title":"Nat. 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