SARS-CoV-2 niches in human placenta revealed by spatial transcriptomics.

Autor:	Barrozo ER; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA., Seferovic MD; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA., Castro ECC; Department of Pathology and Immunology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA., Major AM; Department of Pathology and Immunology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA., Moorshead DN; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA; Immunology and Microbiology Graduate Program, Baylor College of Medicine, Houston, TX, USA., Jochum MD; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA., Rojas RF; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA., Shope CD; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA., Aagaard KM; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA. Electronic address: aagaardt@bcm.edu.
Jazyk:	angličtina
Zdroj:	Med (New York, N.Y.) [Med] 2023 Sep 08; Vol. 4 (9), pp. 612-634.e4. Date of Electronic Publication: 2023 Jul 08.
DOI:	10.1016/j.medj.2023.06.003
Abstrakt:	Background: Functional placental niches are presumed to spatially separate maternal-fetal antigens and restrict the vertical transmission of pathogens. We hypothesized a high-resolution map of placental transcription could provide direct evidence for niche microenvironments with unique functions and transcription profiles. Methods: We utilized Visium Spatial Transcriptomics paired with H&E staining to generate 17,927 spatial transcriptomes. By integrating these spatial transcriptomes with 273,944 placental single-cell and single-nuclei transcriptomes, we generated an atlas composed of at least 22 subpopulations in the maternal decidua, fetal chorionic villi, and chorioamniotic membranes. Findings: Comparisons of placentae from uninfected healthy controls (n = 4) with COVID-19 asymptomatic (n = 4) and symptomatic (n = 5) infected participants demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection in syncytiotrophoblasts occurred in both the presence and the absence of maternal clinical disease. With spatial transcriptomics, we found that the limit of detection for SARS-CoV-2 was 1/7,000 cells, and placental niches without detectable viral transcripts were unperturbed. In contrast, niches with high SARS-CoV-2 transcript levels were associated with significant upregulation in pro-inflammatory cytokines and interferon-stimulated genes, altered metallopeptidase signaling (TIMP1), with coordinated shifts in macrophage polarization, histiocytic intervillositis, and perivillous fibrin deposition. Fetal sex differences in gene expression responses to SARS-CoV-2 were limited, with confirmed mapping limited to the maternal decidua in males. Conclusions: High-resolution placental transcriptomics with spatial resolution revealed dynamic responses to SARS-CoV-2 in coordinate microenvironments in the absence and presence of clinically evident disease. Funding: This work was supported by the NIH (R01HD091731 and T32-HD098069), NSF (2208903), the Burroughs Welcome Fund and the March of Dimes Preterm Birth Research Initiatives, and a Career Development Award from the American Society of Gene and Cell Therapy. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu