Impaired erythroid maturation in murine embryos upon loss of the preeclampsia-associated serine protease prostasin Prostasin loss impairs erythropoiesis
4 affiliations
- 1Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland
- 2Institute of Anatomy, Stem Cell Biology, University of Zurich, Zurich, Switzerland
- 3Hematology Service, Departments of Clinical Oncology and Laboratory Medicine and Pathology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
- 4Department of Fundamental Oncology, University of Lausanne, Lausanne, Switzerland
Abstract
In humans, the membrane-bound serine protease prostasin encoded by Prss8 is associated with preeclampsia, a gestational hypertension disorder affecting blood supply of the placenta. Deficiency of Prss8 in mice resulted in embryonic lethality by embryonic day (E) 14.5 and impaired maturation of placental labyrinth. We found in Prss8-/- embryos at E11.5 and E12.5 a reduced frequency of both circulating primitive and erythro-myeloid progenitor (EMP)-derived definitive erythroblasts in the yolk sac, placenta and fetal liver. Single-cell RNA sequencing analyses revealed a downregulation of fetal hemoglobin genes and an upregulation of ribosomal genes in primitive erythroid cells of Prss8-/- embryos, indicating a defective erythroid maturation. We suggest that prostasin regulates primitive erythropoiesis in a cell-extrinsic manner, since its expression was absent in circulating erythroid cells. Indeed, the yolk sac vascular remodeling of Prss8-/- embryos was impaired as evidenced by reduced vessel branching and junctions, likely affecting placenta vascularization and contributing to embryonic demise. Our findings unveil a novel role for prostasin during developmental erythropoiesis and vascular patterning and provide insight into how Prss8 dysregulation may contribute to placental pathologies such as preeclampsia.
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BibTeX
@article{carlo2026impaired,
title = {{Impaired erythroid maturation in murine embryos upon loss of the preeclampsia-associated serine protease prostasin Prostasin loss impairs erythropoiesis}},
author = {Sara Di Carlo and Adrian Salas-Bastos and Mariela Castelblanco Castelblanco and Muriel Auberson and Dongmei Wang and Marie Rumpler and Malaury Tournier and Olivier Staub and Lukas Sommer and Silvia Ferreira Lopes and Ana Jiménez Sànchez and Olaia Naveiras and Edith Hummler},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0360958},
url = {https://doi.org/10.1371/journal.pone.0360958},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Impaired erythroid maturation in murine embryos upon loss of the preeclampsia-associated serine protease prostasin Prostasin loss impairs erythropoiesis
AU - Sara Di Carlo
AU - Adrian Salas-Bastos
AU - Mariela Castelblanco Castelblanco
AU - Muriel Auberson
AU - Dongmei Wang
AU - Marie Rumpler
AU - Malaury Tournier
AU - Olivier Staub
AU - Lukas Sommer
AU - Silvia Ferreira Lopes
AU - Ana Jiménez Sànchez
AU - Olaia Naveiras
AU - Edith Hummler
PY - 2026
DA - 2026/10/16
JO - PLOS One
DO - 10.1371/journal.pone.0360958
UR - https://doi.org/10.1371/journal.pone.0360958
AB - In humans, the membrane-bound serine protease prostasin encoded by Prss8 is associated with preeclampsia, a gestational hypertension disorder affecting blood supply of the placenta. Deficiency of Prss8 in mice resulted in embryonic lethality by embryonic day (E) 14.5 and impaired maturation of placental labyrinth. We found in Prss8-/- embryos at E11.5 and E12.5 a reduced frequency of both circulating primitive and erythro-myeloid progenitor (EMP)-derived definitive erythroblasts in the yolk sac, placenta and fetal liver. Single-cell RNA sequencing analyses revealed a downregulation of fetal hemoglobin genes and an upregulation of ribosomal genes in primitive erythroid cells of Prss8-/- embryos, indicating a defective erythroid maturation. We suggest that prostasin regulates primitive erythropoiesis in a cell-extrinsic manner, since its expression was absent in circulating erythroid cells. Indeed, the yolk sac vascular remodeling of Prss8-/- embryos was impaired as evidenced by reduced vessel branching and junctions, likely affecting placenta vascularization and contributing to embryonic demise. Our findings unveil a novel role for prostasin during developmental erythropoiesis and vascular patterning and provide insight into how Prss8 dysregulation may contribute to placental pathologies such as preeclampsia.
SN - 1932-6203
ER -