2. Academic Validation
  3. Establishment of bovine extraembryonic endoderm stem cells enables efficient blastoid formation

Establishment of bovine extraembryonic endoderm stem cells enables efficient blastoid formation

  • Cell Rep. 2025 Jun 24;44(6):115707. doi: 10.1016/j.celrep.2025.115707.
Hao Ming 1,  Giovanna Nascimento Scatolin 1,  Oscar Alejandro Ojeda-Rojas 2,  Zongliang Jiang 3
Affiliations

Affiliations

  • 1 Department of Animal Sciences, Genetics Institute, University of Florida, Gainesville, FL 32610, USA.
  • 2 Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
  • 3 Department of Animal Sciences, Genetics Institute, University of Florida, Gainesville, FL 32610, USA. Electronic address: z.jiang1@ufl.edu.
PMID: 40402743 DOI: 10.1016/j.celrep.2025.115707
Abstract

Extraembryonic endoderm stem cells (XENs) resemble the primitive endoderm of blastocyst and provide valuable alternatives for understanding hypoblast development and building stem cell-based embryo models. Here, we report that a chemical cocktail (FGF4, BMP4, IL-6, XAV939, and A83-01) enables the de novo derivation and long-term culture of bovine XENs (bXENs) from blastocysts. Transcriptomic and epigenomic analyses confirm the identity of bXENs and reveal that bXENs resemble the hypoblast lineages of early bovine peri-implantation embryos. Furthermore, we show that bXENs maintain the stemness of expanded embryonic stem cells (EPSCs) and prevent them from undergoing differentiation. The chemical cocktail sustaining bXENs also facilitates the growth of epiblasts in developing pre-implantation embryos. Finally, 3D assembly of bXENs with bovine EPSCs and trophoblast stem cells enables efficient generation of blastoids that resemble blastocysts. bXENs and blastoids established here represent accessible in vitro models for understanding embryogenesis and improving reproductive efficiency in domestic livestock.

Keywords

CP: Stem cell research; EPSC; TSC; XEN; assisted reproductive technology; blastocyst; blastoid; bovine; epiblast; hypoblast; trophoblast.

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