{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:56:36Z","timestamp":1790751396313,"version":"4.1.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Gestational diabetes mellitus (GDM) is a common pregnancy complication which could induce immune dysfunction. Although intrauterine hyperglycemia impairs fetal immune development, its cell-type specific effects on neonatal immune cells, and cell\u2011cell communication remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this pilot study, we performed integrated 5\u2032 single\u2011cell RNA sequencing and TCR repertoire analysis of cord blood mononuclear cells from two GDM and one type 2 diabetes mellitus (T2DM) mother\u2013neonate pairs, with public healthy cord blood data (GSE157007) as controls. After quality control, 50,656 cells were analyzed using Seurat, scRepertoire, SCENIC, Monocle 2, decoupleR, and CellChat.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Myeloid lineage expansion and reduced naive T\u2011cell proportions have been found in hyperglycemia\u2011exposed cord blood. TCR analysis revealed mild clonal diversity compression, a shift toward shorter CDR3 lengths, and fewer ultralong CDR3 sequences in hyperglycemia\u2011exposed cord blood. The Tpex\u2011like cell population, which co\u2011expresses stemness markers (TCF7, BACH2), early development markers of T cells (IKZF1, IKZF2) and the pre\u2011exhaustion transcription factor TOX, was enriched in cord blood from GDM and T2DM neonates. This subset displayed elevated activity of TGF-\u03b2, MAPK and PI3K signaling pathways and predominantly resided within unexpanded T cell clonotypes. Pseudotime trajectory profiling indicates that Tpex-like cells reside at an intermediate differentiation state between precursor and effector T\u2011cell populations. Cell communication analysis indicated increased immune interaction strength in GDM cord blood, with enrichment of pro\u2011inflammatory pathways (SEMA4, IL\u201116, SIRP), whereas homeostatic pathways (LAIR1, GALECTIN) dominated in healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>We characterized multi-layered neonatal immune dysregulation observed in the setting of GDM\u2011associated intrauterine hyperglycemia. Tpex\u2011like cells represent a candidate cellular state linked to early immune changes in GDM offspring. We firstly identified candidate molecular signatures for subsequent mechanistic and translational exploration. These pilot findings require validation in larger independent cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1924940","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:05:47Z","timestamp":1790748347000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated single-cell multi-omics analysis delineates neonatal immune dysregulation associated with gestational diabetes mellitus"],"prefix":"10.3389","volume":"17","author":[{"given":"Renke","family":"He","sequence":"first","affiliation":[{"name":"Department of Hematology, First Affiliated Hospital of Jinan University","place":["Guangzhou, China"]},{"name":"Shantou Central Hospital, Shantou Clinical Medical College of Jinan University","place":["Shantou, Guangdong, China"]},{"name":"Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, 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