TY - JOUR
KW - Organogenesis
KW - Systems analysis
AU - Johain R. Ounadjela
AU - Ke Zhang
AU - Koseki J. Kobayashi-Kirschvink
AU - Kang Jin
AU - Andrew J. C. Russell
AU - Andreas I. Lackner
AU - Claire Callahan
AU - Francesca Viggiani
AU - Kushal K. Dey
AU - Karthik Jagadeesh
AU - Theresa Maxian
AU - Anna-Maria Prandstetter
AU - Naeem Nadaf
AU - Qiyu Gong
AU - Ruth Raichur
AU - Morgan L. Zvezdov
AU - Mingyang Hui
AU - Mattew Simpson
AU - Xinwen Liu
AU - Wei Min
AU - Martin Knöfler
AU - Fei Chen
AU - Sandra Haider
AU - Jian Shu
AB - Successful pregnancy relies directly on the placenta’s complex, dynamic, gene-regulatory networks. Disruption of this vast collection of intercellular and intracellular programs leads to pregnancy complications and developmental defects. In the present study, we generated a comprehensive, spatially resolved, multimodal cell census elucidating the molecular architecture of the first trimester human placenta. We utilized paired single-nucleus (sn)ATAC (assay for transposase accessible chromatin) sequencing and RNA sequencing (RNA-seq), spatial snATAC-seq and RNA-seq, and in situ sequencing and hybridization mapping of transcriptomes at molecular resolution to spatially reconstruct the joint epigenomic and transcriptomic regulatory landscape. Paired analyses unraveled intricate tumor-like gene expression and transcription factor motif programs potentially sustaining the placenta in a hostile uterine environment; further investigation of gene-linked cis-regulatory elements revealed heightened regulatory complexity that may govern trophoblast differentiation and placental disease risk. Complementary spatial mapping techniques decoded these programs within the placental villous core and extravillous trophoblast cell column architecture while simultaneously revealing niche-establishing transcriptional elements and cell–cell communication. Finally, we computationally imputed genome-wide, multiomic single-cell profiles and spatially characterized the placental chromatin accessibility landscape. This spatially resolved, single-cell multiomic framework of the first trimester human placenta serves as a blueprint for future studies on early placental development and pregnancy.
BT - Nature Medicine
DA - 2024-11-20
DO - 10.1038/s41591-024-03073-9
LA - en
N2 - Successful pregnancy relies directly on the placenta’s complex, dynamic, gene-regulatory networks. Disruption of this vast collection of intercellular and intracellular programs leads to pregnancy complications and developmental defects. In the present study, we generated a comprehensive, spatially resolved, multimodal cell census elucidating the molecular architecture of the first trimester human placenta. We utilized paired single-nucleus (sn)ATAC (assay for transposase accessible chromatin) sequencing and RNA sequencing (RNA-seq), spatial snATAC-seq and RNA-seq, and in situ sequencing and hybridization mapping of transcriptomes at molecular resolution to spatially reconstruct the joint epigenomic and transcriptomic regulatory landscape. Paired analyses unraveled intricate tumor-like gene expression and transcription factor motif programs potentially sustaining the placenta in a hostile uterine environment; further investigation of gene-linked cis-regulatory elements revealed heightened regulatory complexity that may govern trophoblast differentiation and placental disease risk. Complementary spatial mapping techniques decoded these programs within the placental villous core and extravillous trophoblast cell column architecture while simultaneously revealing niche-establishing transcriptional elements and cell–cell communication. Finally, we computationally imputed genome-wide, multiomic single-cell profiles and spatially characterized the placental chromatin accessibility landscape. This spatially resolved, single-cell multiomic framework of the first trimester human placenta serves as a blueprint for future studies on early placental development and pregnancy.
PY - 2024
SP - 1
EP - 14
T2 - Nature Medicine
TI - Spatial multiomic landscape of the human placenta at molecular resolution
UR - https://www.nature.com/articles/s41591-024-03073-9
Y2 - 2024-11-26
SN - 1546-170X
ER -