Human organoid systems in modeling reproductive tissue development, function, and disease DOI Open Access
Sandra Haider, Alexander G. Beristain

Human Reproduction, Journal Year: 2023, Volume and Issue: 38(8), P. 1449 - 1463

Published: April 29, 2023

Abstract Research focused on human reproductive biology has primarily relied upon clinical samples affording mainly descriptive studies with limited implementation of functional or mechanistic understanding. More importantly, restricted access to embryonic material necessitated the use animals, rats and mice, short-term primary cell cultures derived from patient material. While developmental processes are generally conserved across mammals, specific features unique reproduction have resulted in development human-based vitro systems designed retain recapitulate key molecular cellular important humans. Of note, major advances 3D epithelial stem cell-based modeling organ been made. These cultures, broadly referred as organoids, enable research aimed at understanding hierarchies controlling differentiation function. Moreover, organoids allow pre-clinical testing pharmacological substances, both safety efficacy standpoints, hold large potential driving aspects personalized medicine that were previously not possible traditional models. In this mini-review, we focus summarizing current state regenerative organoid culture female male tracts model development, maintenance, Specifically, will introduce models ovary/fallopian tube, endometrium, cervix, prostate gland, testes. We also describe pre-implanting blastocyst trophoblast, its extraembryonic trophectoderm central fetal, maternal, overall pregnancy health. foundational leading their outline utility well limitations common many these platforms.

Language: Английский

Spatial multiomics map of trophoblast development in early pregnancy DOI Creative Commons
Anna Arutyunyan, Kenny Roberts, Kevin Troulé

et al.

Nature, Journal Year: 2023, Volume and Issue: 616(7955), P. 143 - 151

Published: March 29, 2023

Abstract The relationship between the human placenta—the extraembryonic organ made by fetus, and decidua—the mucosal layer of uterus, is essential to nurture protect fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate decidua, transforming maternal arteries into high-conductance vessels 1 . Defects in invasion arterial transformation established early pregnancy underlie common disorders such as pre-eclampsia 2 Here we have generated a spatially resolved multiomics single-cell atlas entire maternal–fetal interface including myometrium, which enables us resolve full trajectory differentiation. We used this cellular map infer possible transcription factors mediating EVT show that they are preserved vitro models differentiation primary organoids 3,4 stem 5 define transcriptomes final cell states invasion: bed giant (fused multinucleated EVTs) endovascular EVTs (which form plugs inside arteries). predict cell–cell communication events contributing formation, model dual role interstitial Together, our data provide comprehensive analysis postimplantation can be inform design experimental placenta

Language: Английский

Citations

146
Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface DOI Creative Commons
Liheng Yang, Eleanor C. Semmes, Cristian Ovies

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Aug. 17, 2022

Infections at the maternal-fetal interface can directly harm fetus and induce complications that adversely impact pregnancy outcomes. Innate immune signaling by both fetal-derived placental trophoblasts maternal decidua must provide antimicrobial defenses this critical without compromising its integrity. Here, we developed matched trophoblast (TO) organoids (DO) from human placentas to define relative contributions of these cells antiviral interface. We demonstrate TO DO basally secrete distinct immunomodulatory factors, including constitutive release type III interferon IFN-λ2 TOs, differentially respond viral infections through induction organoid-specific factors. Finally, differential susceptibility innate cytomegalovirus (HCMV) develop a co-culture model which showed trophoblast-derived factors protect decidual HCMV infection. Our findings establish as ex vivo models study vertically transmitted highlight differences in decidua.

Language: Английский

Citations

72
Local immune recognition of trophoblast in early human pregnancy: controversies and questions DOI Open Access
Ashley Moffett,

Norman Shreeve

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(4), P. 222 - 235

Published: Oct. 3, 2022

Language: Английский

Citations

71
3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages DOI Creative Commons
Rowan M. Karvas, Joseph E. Zemke,

Syed Shahzaib Ali

et al.

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(9), P. 1148 - 1165.e7

Published: Sept. 1, 2023

Naive human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures ("blastoids") that model lineage segregation in pre-implantation embryo. However, extent which blastoids can recapitulate defining features of post-implantation development remains unexplored. Here, we report cultured on thick three-dimensional (3D) extracellular matrices capture hallmarks early development, including epiblast lumenogenesis, rapid expansion and diversification trophoblast lineages, robust invasion extravillous by day 14. Extended blastoid culture results localized activation primitive streak marker TBXT emergence embryonic germ layers 21. We also show modulation WNT signaling alters balance between fates blastoids. This work demonstrates 3D-cultured offer a continuous integrated vitro system extraembryonic from gastrulation stages.

Language: Английский

Citations

57
Single-nucleus multi-omic profiling of human placental syncytiotrophoblasts identifies cellular trajectories during pregnancy DOI Creative Commons
Meijiao Wang, Yawei Liu,

Run Sun

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(2), P. 294 - 305

Published: Jan. 24, 2024

Abstract The human placenta has a vital role in ensuring successful pregnancy. Despite the growing body of knowledge about its cellular compositions and functions, there been limited research on heterogeneity billions nuclei within syncytiotrophoblast (STB), multinucleated entity primarily responsible for placental function. Here we conducted integrated single-nucleus RNA sequencing ATAC analyses placentas from early late Our findings demonstrate dynamic developmental trajectories STB their correspondence with trophoblast stem cell (hTSC)-derived STB. Furthermore, identified transcription factors associated diverse nuclear lineages through gene regulatory networks experimentally confirmed function hTSC organoid-derived STBs. Together, our data provide insights into represent valuable resource interpreting pregnancy complications.

Language: Английский

Citations

32
Trophoblast stem cell-based organoid models of the human placental barrier DOI Creative Commons
Takeshi Hori, Hiroaki Okae, Shun Shibata

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 8, 2024

Abstract Human placental villi have essential roles in producing hormones, mediating nutrient and waste exchange, protecting the fetus from exposure to xenobiotics. trophoblast organoids that recapitulate structure of could provide an important vitro tool understand development transplacental passage However, such do not currently exist. Here we describe generation using human stem (TS) cells. Following treatment with three kinds culture medium, TS cells form spherical a single outer layer syncytiotrophoblast (ST) display barrier function. Furthermore, develop column-type ST model based on condition organoids. The bottom membrane column is almost entirely covered syndecan 1-positive integrity maturation levels are confirmed by measuring transepithelial/transendothelial electrical resistance (TEER) amount chorionic gonadotropin. Further analysis reveals can be used derive apparent permeability coefficients compounds. In addition providing suite tools for study development, our models allow evaluation compound transfer toxicity, which will facilitate drug development.

Language: Английский

Citations

30
A Comprehensive Human Embryogenesis Reference Tool using Single-Cell RNA-Sequencing Data DOI Open Access
Cheng Zhao, Álvaro Plaza Reyes,

John P. Schell

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: May 7, 2021

Summary Stem cell-based embryo models offer unprecedented experimental tools for studying early human development. The usefulness of hinges on their molecular, cellular and structural fidelities to in vivo counterparts. To authenticate models, single-cell RNA-sequencing has been utilised unbiased transcriptional profiling. However, a well-organised integrated dataset, serving as universal reference benchmarking remains unavailable. Herein, we developed such reference, through integration six published datasets covering developmental stages from the zygote gastrula. Lineage annotations are contrasted validated with available non-human primate datasets. Using stabilised UMAP constructed web tool, where query can be projected annotated predicted cell identities. this examined several recent highlighting risk misannotation when relevant references lacking.

Language: Английский

Citations

66
Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells DOI Creative Commons
Thi Xuan Ai Pham, Amitesh Panda, Harunobu Kagawa

et al.

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(9), P. 1346 - 1365.e10

Published: Sept. 1, 2022

A hallmark of primate postimplantation embryogenesis is the specification extraembryonic mesoderm (EXM) before gastrulation, in contrast to rodents where this tissue formed only after gastrulation. Here, we discover that naive human pluripotent stem cells (hPSCs) are competent differentiate into EXM (EXMCs). EXMCs specified by inhibition Nodal signaling and GSK3B, maintained mTOR BMP4 activity, their transcriptome epigenome closely resemble monkey embryo EXM. mesenchymal, can arise from an epiblast intermediate, capable self-renewal. Thus, arising via primate-specific between implantation gastrulation be modeled vitro. We also find most rare off-target within blastoids triple (Kagawa et al., 2021) correspond EXMCs. Our study impacts our ability model molecular mechanisms early related defects.

Language: Английский

Citations

59
COVID-19 and pregnancy: clinical outcomes; mechanisms, and vaccine efficacy DOI Creative Commons
Deepak Kumar, Sonam Verma, Indira U. Mysorekar

et al.

Translational research, Journal Year: 2022, Volume and Issue: 251, P. 84 - 95

Published: Aug. 12, 2022

Language: Английский

Citations

49
A comprehensive review of human trophoblast fusion models: recent developments and challenges DOI Creative Commons
Xia Li, Zhuo‐Hang Li, Ying-Xiong Wang

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Oct. 10, 2023

As an essential component of the maternal-fetal interface, placental syncytiotrophoblast layer contributes to a successful pregnancy by secreting hormones necessary for pregnancy, transporting nutrients, mediating gas exchange, balancing immune tolerance, and resisting pathogen infection. Notably, deficiency in mononuclear trophoblast cells fusing into multinucleated has been linked adverse outcomes, such as preeclampsia, fetal growth restriction, preterm birth, stillbirth. Despite availability many models study fusion, there exists notable disparity from ideal model, limiting deeper exploration development. Here, we reviewed existing employed investigation human fusion several aspects, including development history, latest progress, advantages, disadvantages, scope application, challenges. The literature searched covers monolayer cell lines, primary trophoblast, explants, stem cells, pluripotent three-dimensional spheres, organoids, placenta-on-a-chip 1938 2023. These diverse have significantly enhanced our comprehension regulation underlying mechanisms placental-related disorders. Through this review, objective is provide readers with thorough understanding models, making it easier select most suitable address specific experimental requirements or scientific inquiries. Establishment application models.

Language: Английский

Citations

34