@article{4681, keywords = {Organogenesis, Systems analysis}, author = {Johain R. Ounadjela and Ke Zhang and Koseki J. Kobayashi-Kirschvink and Kang Jin and Andrew J. C. Russell and Andreas I. Lackner and Claire Callahan and Francesca Viggiani and Kushal K. Dey and Karthik Jagadeesh and Theresa Maxian and Anna-Maria Prandstetter and Naeem Nadaf and Qiyu Gong and Ruth Raichur and Morgan L. Zvezdov and Mingyang Hui and Mattew Simpson and Xinwen Liu and Wei Min and Martin Knöfler and Fei Chen and Sandra Haider and Jian Shu}, title = {Spatial multiomic landscape of the human placenta at molecular resolution}, abstract = {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.}, year = {2024}, journal = {Nature Medicine}, pages = {1-14}, month = {2024-11-20}, issn = {1546-170X}, url = {https://www.nature.com/articles/s41591-024-03073-9}, doi = {10.1038/s41591-024-03073-9}, language = {en}, }