The diversity of trophoblast cells and niches of placenta accreta spectrum disorders revealed by single-cell RNA sequencing

Jingmei Ma; Yawei Liu; Zhirong Guo; Run Sun; Xinrui Yang; Weiran Zheng; Yongdan Ma; Yin Rong; Hongmei Wang; Huixia Yang; Zhenyu Xiao

doi:10.3389/fcell.2022.1044198

The diversity of trophoblast cells and niches of placenta accreta spectrum disorders revealed by single-cell RNA sequencing

Front Cell Dev Biol. 2022 Nov 7:10:1044198. doi: 10.3389/fcell.2022.1044198. eCollection 2022.

Authors

Jingmei Ma^{1

2

3}, Yawei Liu^{1

4

5

6

7}, Zhirong Guo^{2

3}, Run Sun^{1

4

5

6}, Xinrui Yang^{2

3}, Weiran Zheng^{2

3}, Yongdan Ma^{2

3}, Yin Rong^{1

4

5

6}, Hongmei Wang^{1

4

5

6}, Huixia Yang^{2

3}, Zhenyu Xiao^{1

4

5

6

8}

Affiliations

¹ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
² Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
³ Beijing Key Laboratory of Maternal Fetal Medicine of Gestational Diabetes Mellitus, Beijing, China.
⁴ Innovation Academy for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
⁵ Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
⁶ University of Chinese Academy of Sciences, Beijing, China.
⁷ Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou Dushu Lake Hospital, Suzhou, China.
⁸ School of Life Science, Beijing Institute of Technology, Beijing, China.

Abstract

Placenta accreta spectrum disorders (PAS) are severe pregnancy complications that occur when extravillous trophoblast cells (EVTs) invade beyond the uterine inner myometrium and are characterized by hypervascularity on prenatal ultrasound and catastrophic postpartum hemorrhage. The potential mechanisms remain incompletely understood. With single-cell RNA-sequencing analysis on the representative invasive parts and the normal part obtained from the same PAS placenta, we profiled the pathological landscape of invasive PAS placenta and deciphered an intensified differentiation pathway from progenitor cytotrophoblasts (CTBs) to EVTs via LAMB4 ⁺ and KRT6A ⁺ CTBs. In the absence of the decidua, the invasive trophoblasts of various differentiation states interacted with ADIRF ⁺ and DES ⁺ maternal stromal cells. The PAS-associated hypervascularity might be due to the enhanced crosstalk of trophoblasts, stromal cells and vascular endothelial cells. Finally, we presented an immune microenvironmental landscape of invasive PAS. The pathogenesis of PAS could be further explored with current resources for future targeted translational studies.

Keywords: pathogenesis; placenta; placenta accreta spectrum; single-cell sequencing; trophoblast.