Protocol for Human Blastoids Modeling Blastocyst Development and Implantation.
J Vis Exp
; (186)2022 08 10.
Article
in En
| MEDLINE
| ID: mdl-36036618
ABSTRACT
A model of the human blastocyst formed from stem cells (blastoid) would support scientific and medical advances. However, its predictive power will depend on its ability to efficiently, timely, and faithfully recapitulate the sequences of blastocyst development (morphogenesis, specification, patterning), and to form cells reflecting the blastocyst stage. Here we show that naïve human pluripotent stem cells cultured in PXGL conditions and then triply inhibited for the Hippo, transforming growth factor- ß, and extracellular signal-regulated kinase pathways efficiently undergo morphogenesis to form blastoids (>70%). Matching with developmental timing (~4 days), blastoids unroll the blastocyst sequence of specification by producing analogs of the trophoblast and epiblast, followed by the formation of analogs of the primitive endoderm and the polar trophoblasts. This results in the formation of cells transcriptionally similar to the blastocyst (>96%) and a minority of post-implantation analogs. Blastoids efficiently pattern by forming the embryonic-abembryonic axis marked by the maturation of the polar region (NR2F2+), which acquires the specific potential to directionally attach to hormonally stimulated endometrial cells, as in utero. Such a human blastoid is a scalable, versatile, and ethical model to study human development and implantation in vitro.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Embryo Implantation
/
Embryonic Development
Type of study:
Prognostic_studies
Aspects:
Ethics
Limits:
Female
/
Humans
Language:
En
Journal:
J Vis Exp
Year:
2022
Document type:
Article