☆ 4.8 Article

Primary decidual zone formation requires Scribble for pregnancy success in mice

NATURE COMMUNICATIONS (2019)

Journal

NATURE COMMUNICATIONS

Volume 10, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP

DOI: 10.1038/s41467-019-13489-4

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Funding

NIH [HD068524, DA006668]
March of Dimes Centre grant [22-FY17-889]
Astellas Foundation for Research on Metabolic Disorder Fellowship
Osamu Hasashi Memorial Foundation
JSPS Overseas Research Fellowship
DFG [CRC1192, CRC1140, CRC 992]
BMBF [01GM1518C]
European Research Council-ERC [616891]
H2020-IMI2 consortium BEAT-DKD
[CRC 1140]

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Abstract

Scribble (Scrib) is a scaffold protein with multifunctional roles in PCP, tight junction and Hippo signaling. This study shows that Scrib is expressed in stromal cells around the implantation chamber following implantation. Stromal cells transform into epithelial-like cells to form the avascular primary decidual zone (PDZ) around the implantation chamber (crypt). The PDZ creates a permeability barrier around the crypt restricting immune cells and harmful agents from maternal circulation to protect embryonic health. The mechanism underlying PDZ formation is not yet known. We found that uterine deletion of Scrib by a Pgr-Cre driver leads to defective PDZ formation and implantation chamber (crypt) formation, compromising pregnancy success. Interestingly, epithelial-specific Scrib deletion by a lactoferrin-Cre (Ltf-Cre) driver does not adversely affect PDZ formation and pregnancy success. These findings provide evidence for a previously unknown function of stromal Scrib in PDZ formation, potentially involving ZO-1 and Hippo signaling.

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Single-cell characterization of self-renewing primary trophoblast organoids as modeling of EVT differentiation and interactions with decidual natural killer cells

Bai-Mei Zhuang, Dan-Dan Cao, Tian-Xi Li, Xiao-Feng Liu, Min-Min Lyu, Si-Dong Wang, Xin-Yuan Cui, Li Wang, Xiao-Lin Chen, Xiao-Li Lin, Cheuk-Lun Lee, Philip C. N. Chiu, William S. B. Yeung, Yuan-Qing Yao

Summary: Our study provides a single-cell atlas for trophoblast organoids (TOs) and explores their applications in extravillous trophoblast (EVT) differentiation and communication with decidual natural killer (dNK) cells. We identified multiple distinct trophoblast states and dNK subpopulations, and found a close resemblance between TO/EVT-TO and human placenta. Transcription factors were found to be essential for controlling EVT differentiation, and ligand-receptor complexes related to cytokines, immunomodulation, and angiogenesis were predicted in dNK-EVT-TO co-cultures. Furthermore, we found that dNK cells can exert effects on EVT causing functionally important expression changes.

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