A New Frontier in Human Development Research: Advanced 3D Gastruloid Models Enable Exploration of Early Lineages

HUMAN GASTRULOIDS REVEAL PRIMORDIAL GERM CELL-LIKE CELLS

A groundbreaking study, led by researchers from the University of Cambridge (A. Surani’s lab) and the Helmholtz Munich (A. Scialdone’s lab), introduces a next-generation in vitro model for human embryonic development. By generating self-organized 3D human gastruloids (hGs) from embryonic stem cells, this research provides a powerful new tool to investigate early human development, particularly the germ line and other key lineages, in unprecedented detail.

These hGs recapitulate critical developmental milestones, mimicking gastrulation by elongating along a rostro-caudal axis and forming the three germ layers. They also exhibit post-gastrulation features, including cardiomyocytes and neuromesodermal progenitors. Their gene expression profiles align with Carnegie stage 7 (CS7) human embryos, making them a valuable model to study aspects of human development that remain largely inaccessible due to ethical constraints surrounding human embryo research.

UNCOVERING GERMLINE ORIGINS: THE ROLE OF THE AMNION

A breakthrough discovery in this study is the emergence of primordial germ cell-like cells (PGCLCs) within these gastruloids without the need for external bone morphogenetic protein (BMP) supplementation, which was previously considered essential for PGCLC formation. Further analysis revealed that mutations in the amniotic marker ISL1 disrupted AMLC and PGCLC formation, but the addition of exogenous BMP restored PGCLCs. Hence, the study identifies amnion-like cells (AMLC) as a likely endogenous source of BMP signaling, which is critical for PGCLC development.

ADVANCED COMPUTATIONAL ANALYSIS OF CELL FATE TRANSITIONS

To gain a deeper understanding of cell lineage trajectories within these models, researchers at Helmholtz Munich employed machine learning-based analysis on single-cell transcriptomic datasets generated from the gastruloids. This approach provided a detailed molecular characterization of the various cell lineages present and their fate transitions over an eight-day time course, offering high-resolution insights into early human development.

EXPANDING THE TOOLKIT FOR HUMAN EMBRYO RESEARCH

This study significantly expands the toolkit of available in vitro models by advancing the gastruloid platform. It provides a reproducible, self-organized, and ethically viable system to investigate early human developmental processes, germline formation, and cell fate decisions. Beyond fundamental research, this model has the potential to inform genetic screening, regenerative medicine, and studies of developmental disorders, pushing the boundaries of what can be explored without relying on human embryos.

By integrating cutting-edge stem cell biology and computational analysis, this collaboration opens new avenues for exploring the earliest stages of human life, offering insights that were previously out of reach.

ORIGINAL PUBLICATION:

Jitesh Neupane*, Gabriele Lubatti*, Theresa Gross-Thebing, Mayra Luisa Ruiz Tejada Segura, Richard Butler, Sargon Gross-Thebing, Sabine Dietmann, Antonio Scialdone† and M Azim Surani†. “The emergence of human primordial germ cell-like cells in stem cells-derived gastruloids”. Science Advances. 2025.