Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy.
Cell Stem Cell
; 31(2): 181-195.e9, 2024 02 01.
Article
en En
| MEDLINE
| ID: mdl-38237587
ABSTRACT
In humans, balanced invasion of trophoblast cells into the uterine mucosa, the decidua, is critical for successful pregnancy. Evidence suggests that this process is regulated by uterine natural killer (uNK) cells, but how they influence reproductive outcomes is unclear. Here, we used our trophoblast organoids and primary tissue samples to determine how uNK cells affect placentation. By locating potential interaction axes between trophoblast and uNK cells using single-cell transcriptomics and in vitro modeling of these interactions in organoids, we identify a uNK cell-derived cytokine signal that promotes trophoblast differentiation at the late stage of the invasive pathway. Moreover, it affects transcriptional programs involved in regulating blood flow, nutrients, and inflammatory and adaptive immune responses, as well as gene signatures associated with disorders of pregnancy such as pre-eclampsia. Our findings suggest mechanisms on how optimal immunological interactions between uNK cells and trophoblast enhance reproductive success.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Útero
/
Trofoblastos Extravellosos
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
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Pregnancy
Idioma:
En
Revista:
Cell Stem Cell
Año:
2024
Tipo del documento:
Article