Human blastoids model blastocyst development and implantation

Abstract

One week after fertilization, human embryos implant into the uterus. This event requires the embryo to form a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model that we called a blastoid1. Here we show that naive human pluripotent stem cells cultured in PXGL medium2 and triply inhibited for the Hippo, TGF-β and ERK pathways efficiently (with more than 70% efficiency) form blastoids generating blastocyst-stage analogues of the three founding lineages (more than 97% trophectoderm, epiblast and primitive endoderm) according to the sequence and timing of blastocyst development. Blastoids spontaneously form the first axis, and we observe that the epiblast induces the local maturation of the polar trophectoderm, thereby endowing blastoids with the capacity to directionally attach to hormonally stimulated endometrial cells, as during implantation. Thus, we propose that such a human blastoid is a faithful, scalable and ethical model for investigating human implantation and development3,4.

A Comprehensive Human Embryogenesis Reference Tool using Single-Cell RNA-Sequencing Data

“…2b-c). Mesoderm-like and unidentified cells can also be found in Yu-Blastoids and to a lesser degree in blastoids from PXGL culture condition (KAG-Blastoids 2 and YAN-Blastoids 3 ; Fig. 1a-b and Extended Data Fig.…”

“…In contrast, all three naïve hPSC-derived blastoids contain expected cell types, with most of the annotated epiblast-like cells (ELC), hypoblast-like cells (HLC), and TLC overlapping with their counterparts in the human embryo. Furthermore, inclusion of transcriptome data from naïve and primed hPSCs as well as trophoblast stem cells representative of post-implantation human trophoblast lineage 2,9 together with the integrated dataset enabled us to explore developmental stages of blastoid cell lineages (Extended Data Fig. 1a).…”

“…1a). Among the naïve hPSC-derived blastoids, those cultured in the PXGL condition (KAG-Blastoids 2 and YAN-Blastoids 3 ) generally comprise cell lineages that align better with those in preimplantation human blastocysts, whereas blastoids generated from hPSCs cultured in the 5i/L/A condition still contain a notable portion of cells resembling those in postimplantation human embryos (Yu-Blastoids 1 ) (Fig. 1b).…”

Human Endometrial Organoids: Recent Research Progress and Potential Applications

“…( Boretto et al, 2017 ; Wanxin Wang et al, 2020 ). As happening in vivo , blastocyst didn’t attach to nonreceptive OFEL ( Kagawa et al, 2022 ).…”

Home Away From Home: Bioengineering Advancements to Mimic the Developmental and Adult Stem Cell Niche

“…Pluripotent stem cells have been employed to generate blastocyst-like structures modeling early embryonic development (Liu et al, 2021;Yanagida et al, 2021;Yu et al, 2021). Blastoids are stem cell-derived models of blastocyst-stage conceptus, which recapitulate the early developmental events such as implantation, cell fate determination, and morphogenesis (Kagawa et al, 2021). Blastocyst-derived stem cells in mice demonstrated the ability to form spatially ordered implantable embryoids exhibiting lumenogenesis, expression markers of mesoderm, primordial germ cell precursors, and endoderm-like tissues in controlled microfluidic systems (Zheng et al, 2019).…”