Expression and Distribution of Src Kinase Lyn in the Placenta of Patients with Preeclampsia
- 1Department of Obstetrics and Gynecology, University of Illinois Chicago, Chicago, IL, 60612, USA
Abstract
Src family kinases (SFKs) constitute a major non-receptor tyrosine kinase class that regulate processes important for pregnancy. We profiled placental SFKs to assess cell-specific expression, tissue localization, and clinical associations in early-onset preeclampsia (PE). Placental SFK transcripts were analyzed using bulk RNA sequencing discovery (GSE203507; n=15 PE, n=15 controls) and external validation (GSE114691; n=40 PE, n=21 controls) cohorts. Single-cell and single-nucleus RNA sequencing atlases mapped cell-specific expression. Computational deconvolution and causal mediation analyses were applied to bulk datasets. Findings were cross-validated by real-time quantitative PCR (qPCR; n=9 early-onset PE, n=7 controls) and immunohistochemistry (IHC). Transcriptomic data showed that LYN was the sole SFK member consistently elevated in early-onset PE placentas across discovery (1.8-fold, FDR<0.01) and validation cohorts (2.2-fold, FDR<0.001). Elevation was verified by qPCR (p<0.0001) and remained significant after adjusting for clinical covariates. Placental LYN abundance correlated positively with maximum antepartum maternal systolic blood pressure (r=0.63, p<0.01). Single-cell transcriptome atlases demonstrated LYN enrichment in myeloid lineages, extravillous trophoblasts, and syncytiotrophoblast (SCT). Deconvolution and mediation analyses indicated that altered tissue composition and increased per-cell expression each accounted for approximately half of the PE-associated LYN increase. IHC localized Lyn protein to Hofbauer macrophages and the apical microvillar SCT membrane in PE placentas. We conclude that placental LYN expression is selectively elevated in early-onset PE and correlates with maternal blood pressure severity. Lyn localization to trophoblasts and placental immune cells suggests potential roles in mediating inflammation and hypoxia-associated signaling in PE pathogenesis.
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BibTeX
@misc{heyman2026expression,
title = {{Expression and Distribution of Src Kinase Lyn in the Placenta of Patients with Preeclampsia}},
author = {T. D. Heyman and I. A. Buhimschi and G. Zhao and B. Medegan Fagla and C. S. Buhimschi and W. E. Ackerman},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.26365934},
url = {https://www.medrxiv.org/content/10.64898/2026.10.19.26365934v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Expression and Distribution of Src Kinase Lyn in the Placenta of Patients with Preeclampsia
AU - T. D. Heyman
AU - I. A. Buhimschi
AU - G. Zhao
AU - B. Medegan Fagla
AU - C. S. Buhimschi
AU - W. E. Ackerman
PY - 2026
DA - 2026/10/19
PB - medRxiv
DO - 10.64898/2026.10.19.26365934
UR - https://www.medrxiv.org/content/10.64898/2026.10.19.26365934v1
AB - Src family kinases (SFKs) constitute a major non-receptor tyrosine kinase class that regulate processes important for pregnancy. We profiled placental SFKs to assess cell-specific expression, tissue localization, and clinical associations in early-onset preeclampsia (PE). Placental SFK transcripts were analyzed using bulk RNA sequencing discovery (GSE203507; n=15 PE, n=15 controls) and external validation (GSE114691; n=40 PE, n=21 controls) cohorts. Single-cell and single-nucleus RNA sequencing atlases mapped cell-specific expression. Computational deconvolution and causal mediation analyses were applied to bulk datasets. Findings were cross-validated by real-time quantitative PCR (qPCR; n=9 early-onset PE, n=7 controls) and immunohistochemistry (IHC). Transcriptomic data showed that LYN was the sole SFK member consistently elevated in early-onset PE placentas across discovery (1.8-fold, FDR<0.01) and validation cohorts (2.2-fold, FDR<0.001). Elevation was verified by qPCR (p<0.0001) and remained significant after adjusting for clinical covariates. Placental LYN abundance correlated positively with maximum antepartum maternal systolic blood pressure (r=0.63, p<0.01). Single-cell transcriptome atlases demonstrated LYN enrichment in myeloid lineages, extravillous trophoblasts, and syncytiotrophoblast (SCT). Deconvolution and mediation analyses indicated that altered tissue composition and increased per-cell expression each accounted for approximately half of the PE-associated LYN increase. IHC localized Lyn protein to Hofbauer macrophages and the apical microvillar SCT membrane in PE placentas. We conclude that placental LYN expression is selectively elevated in early-onset PE and correlates with maternal blood pressure severity. Lyn localization to trophoblasts and placental immune cells suggests potential roles in mediating inflammation and hypoxia-associated signaling in PE pathogenesis.
ER -