Single-cell atlas of circulating immune cells reveals a dynamic landscape over the first two months of age
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ABSTRACT: Extremely premature infants (EPI), or those born prior to 30 weeks’ gestation, are highly susceptible to infection and inflammation. The impact of pre- and postnatal exposures on the immune response is poorly understood. We analyzed over 200, 000 circulating immune cells from 100-200L of whole blood collected from 25 donors including longitudinal samples from 10 EPI that were compared to healthy adults and to cord blood from term and preterm infants. We performed single-cell RNA-, T- and B-cell receptor sequencing, and phosphoprotein mass cytometry from matched samples and proteomics on dried blood spots from the same donors. Our data defined the trajectory of circulating T-, B-, myeloid and natural killer cells. Peripheral T cell development rapidly progressed over the first month of EPI’s life with an increase in the proportion of naïve CD4+, regulatory, and cycling T cells, accompanied by increased STAT5 signaling. Simultaneously, the transcription of IL2, which is essential for T cell activation and proliferation, increased in the lymphocytes. T cell repertoire diversity, clonality and gene usage increased rapidly over the first 60 days of life in EPI. CD38hi B cells were directly proportional to gestational age at birth. Interestingly, in utero exposure to inflammation (chorioamnionitis) altered the abundance, transcriptome and signaling of circulating T cells and monocytes specifically at 1 month of life in EPIs. Finally, we demonstrate the feasibility of a robust multi-omic longitudinal analysis in EPI from minute amounts of blood, developing a resource for studying the impact of early life exposures on immune development.
ORGANISM(S): Homo sapiens
PROVIDER: GSE271413 | GEO | 2025/02/05
REPOSITORIES: GEO
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