02859nas a2200445   4500000000100000000000100001008004100002260001500043653001800058653002100076100002400097700001300121700003500134700001300169700002500182700002300207700002000230700002300250700001800273700002200291700001900313700002800332700001600360700001400376700001700390700002200407700001700429700001900446700001500465700001200480700002000492700001300512700001800525700001300543245007800556856005500634300000900689520170100698022001402399       2024                            d  c2024-11-2010aOrganogenesis10aSystems analysis1 aJohain R. Ounadjela1 aKe Zhang1 aKoseki J. Kobayashi-Kirschvink1 aKang Jin1 aAndrew J. C. Russell1 aAndreas I. Lackner1 aClaire Callahan1 aFrancesca Viggiani1 aKushal K. Dey1 aKarthik Jagadeesh1 aTheresa Maxian1 aAnna-Maria Prandstetter1 aNaeem Nadaf1 aQiyu Gong1 aRuth Raichur1 aMorgan L. Zvezdov1 aMingyang Hui1 aMattew Simpson1 aXinwen Liu1 aWei Min1 aMartin Knöfler1 aFei Chen1 aSandra Haider1 aJian Shu00aSpatial multiomic landscape of the human placenta at molecular resolution  uhttps://www.nature.com/articles/s41591-024-03073-9  a1-143 aSuccessful 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.  a1546-170X