Single-nucleus RNA sequencing reveals distinct pathophysiological trophoblast signatures in spontaneous preterm birth subtypes
Abstract Spontaneous preterm birth (sPTB) poses significant challenges, affecting neonatal health and neurodevelopmental outcomes worldwide. The specific effects of placental trophoblasts on the pathological development of sPTB subtypes—preterm premature rupture of fetal membranes (pPROM) and sponta...
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BMC
2025-01-01
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| Series: | Cell & Bioscience |
| Online Access: | https://doi.org/10.1186/s13578-024-01343-0 |
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| author | Cherilyn Uhm Jianlei Gu Weina Ju Stephanie Pizzella Hande Oktay Joyce Yao-Chun Peng Sararose Guariglia Yong Liu Hongyu Zhao Yong Wang Ramkumar Menon Nanbert Zhong |
| author_facet | Cherilyn Uhm Jianlei Gu Weina Ju Stephanie Pizzella Hande Oktay Joyce Yao-Chun Peng Sararose Guariglia Yong Liu Hongyu Zhao Yong Wang Ramkumar Menon Nanbert Zhong |
| author_sort | Cherilyn Uhm |
| collection | DOAJ |
| description | Abstract Spontaneous preterm birth (sPTB) poses significant challenges, affecting neonatal health and neurodevelopmental outcomes worldwide. The specific effects of placental trophoblasts on the pathological development of sPTB subtypes—preterm premature rupture of fetal membranes (pPROM) and spontaneous preterm labor (sPTL)—are not fully understood, making it crucial to uncover these impacts for the development of effective therapeutic strategies. Using single-nucleus RNA sequencing, we investigated transcriptomic and cellular differences at the maternal–fetal interface in pPROM and sPTL placentas. Our findings revealed distinct trophoblast compositions with pPROM characterized predominantly by extravillous trophoblasts (EVTs), while sPTL showed an abundance of syncytiotrophoblasts (STBs). Through cell differentiation and cell-to-cell communication analyses, other distinguishing factors were also found. In pPROM, heightened inflammation, oxidative stress, and vascular dysregulation with key pathways including tumor necrosis factor signaling, matrix metalloproteinase activation, and integrin-mediated cell adhesion, highlighted an invasive EVT profile potentially driven by hypoxic conditions and immune cell recruitment. In contrast, sPTL was marked by increased smooth muscle contraction, vascular remodeling, and altered signaling dynamics involving fibroblasts, including TGF-β and WNT pathways. Our study highlights the critical need to distinguish sPTB subtypes to improve diagnostic precision and therapeutic targeting. The molecular insights gained provide a foundation for future investigations aimed at functional validation of key pathways and exploration of trophoblasts on the development of sPTB. Ultimately, these findings pave the way for more personalized and effective interventions to mitigate adverse outcomes associated with preterm birth. |
| format | Article |
| id | doaj-art-9ff491be548f4eeaa56242f65d613c7a |
| institution | Kabale University |
| issn | 2045-3701 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj-art-9ff491be548f4eeaa56242f65d613c7a2025-01-12T12:41:26ZengBMCCell & Bioscience2045-37012025-01-0115111410.1186/s13578-024-01343-0Single-nucleus RNA sequencing reveals distinct pathophysiological trophoblast signatures in spontaneous preterm birth subtypesCherilyn Uhm0Jianlei Gu1Weina Ju2Stephanie Pizzella3Hande Oktay4Joyce Yao-Chun Peng5Sararose Guariglia6Yong Liu7Hongyu Zhao8Yong Wang9Ramkumar Menon10Nanbert Zhong11New York State Institute for Basic Research in Developmental DisabilitiesSchool of Public Health, Yale UniversityNew York State Institute for Basic Research in Developmental DisabilitiesDepartment of Obstetrics and Gynecology, School of Medicine, Washington UniversityNew York State Institute for Basic Research in Developmental DisabilitiesSingulomics CorporationNew York State Institute for Basic Research in Developmental DisabilitiesNew York State Institute for Basic Research in Developmental DisabilitiesSchool of Public Health, Yale UniversityDepartment of Obstetrics and Gynecology, School of Medicine, Washington UniversityThe University of Texas Medical Branch at GalvestonNew York State Institute for Basic Research in Developmental DisabilitiesAbstract Spontaneous preterm birth (sPTB) poses significant challenges, affecting neonatal health and neurodevelopmental outcomes worldwide. The specific effects of placental trophoblasts on the pathological development of sPTB subtypes—preterm premature rupture of fetal membranes (pPROM) and spontaneous preterm labor (sPTL)—are not fully understood, making it crucial to uncover these impacts for the development of effective therapeutic strategies. Using single-nucleus RNA sequencing, we investigated transcriptomic and cellular differences at the maternal–fetal interface in pPROM and sPTL placentas. Our findings revealed distinct trophoblast compositions with pPROM characterized predominantly by extravillous trophoblasts (EVTs), while sPTL showed an abundance of syncytiotrophoblasts (STBs). Through cell differentiation and cell-to-cell communication analyses, other distinguishing factors were also found. In pPROM, heightened inflammation, oxidative stress, and vascular dysregulation with key pathways including tumor necrosis factor signaling, matrix metalloproteinase activation, and integrin-mediated cell adhesion, highlighted an invasive EVT profile potentially driven by hypoxic conditions and immune cell recruitment. In contrast, sPTL was marked by increased smooth muscle contraction, vascular remodeling, and altered signaling dynamics involving fibroblasts, including TGF-β and WNT pathways. Our study highlights the critical need to distinguish sPTB subtypes to improve diagnostic precision and therapeutic targeting. The molecular insights gained provide a foundation for future investigations aimed at functional validation of key pathways and exploration of trophoblasts on the development of sPTB. Ultimately, these findings pave the way for more personalized and effective interventions to mitigate adverse outcomes associated with preterm birth.https://doi.org/10.1186/s13578-024-01343-0 |
| spellingShingle | Cherilyn Uhm Jianlei Gu Weina Ju Stephanie Pizzella Hande Oktay Joyce Yao-Chun Peng Sararose Guariglia Yong Liu Hongyu Zhao Yong Wang Ramkumar Menon Nanbert Zhong Single-nucleus RNA sequencing reveals distinct pathophysiological trophoblast signatures in spontaneous preterm birth subtypes Cell & Bioscience |
| title | Single-nucleus RNA sequencing reveals distinct pathophysiological trophoblast signatures in spontaneous preterm birth subtypes |
| title_full | Single-nucleus RNA sequencing reveals distinct pathophysiological trophoblast signatures in spontaneous preterm birth subtypes |
| title_fullStr | Single-nucleus RNA sequencing reveals distinct pathophysiological trophoblast signatures in spontaneous preterm birth subtypes |
| title_full_unstemmed | Single-nucleus RNA sequencing reveals distinct pathophysiological trophoblast signatures in spontaneous preterm birth subtypes |
| title_short | Single-nucleus RNA sequencing reveals distinct pathophysiological trophoblast signatures in spontaneous preterm birth subtypes |
| title_sort | single nucleus rna sequencing reveals distinct pathophysiological trophoblast signatures in spontaneous preterm birth subtypes |
| url | https://doi.org/10.1186/s13578-024-01343-0 |
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