Cell crowding in early human embryos influences cell identity decisions, finds a new culture system

Published in Journal Science Advances, the research revealed that cell density in early human embryos affects whether cells become extra-embryonic or contribute to the embryo, forming skin, hair, and nails.

The amniotic ectoderm, forming the embryo's surrounding membrane, provides crucial signals for human embryo development, yet its origin remains partially understood. Surface ectoderm, responsible for skin and related structures, shares similarities with amniotic ectoderm but is not fully elucidated in its development. Despite differences, both tissues exhibit early specialization and common biological features.

Dr. Shota Nakanoh devised tailored culture conditions for human pluripotent stem cells (hPSCs), discovering that specific supplements prompted their differentiation into amniotic ectoderm. Utilizing a co-culture method, he verified the ability of these cells to initiate gastrulation. Single-cell RNA sequencing analysis indicated a differentiation pathway from surface ectoderm to amniotic ectoderm.

Comparison with primate embryo data confirmed cultured cells' similarity to embryonic tissues. Cell density determined cell fate, favoring amniotic ectoderm under specific conditions and surface ectoderm under high density. The study also found cells resembling extra-embryonic mesoderm. Accurate amnion formation is vital for mimicking human embryo development in stem cell-based models, allowing study beyond technical and regulatory limitations on human embryo research.

“We have only recently begun to explore the generation of amnion during human development. These findings advance our understanding on how to generate extra-embryonic cells in the lab in vitro, and sheds light on the mechanisms that drive the formation of cell types at the stages that correspond to the ‘black box’ of human development. Given the growing interest in using stem cell embryo models as proxies of human embryos, this work provides more knowledge for the generation of successful integrated models.” said Dr Teresa Rayon, group leader in the Institute’s Epigenetics research programme.

“Our culture system also generates extra-embryonic mesoderm, another tissue not studied well in human embryos. It will provide better understanding of human development and could improve our knowledge about diseases affecting first step of foetal life. This work also opens the door for new studies regarding the role of cellular density in cell fate decision.” concluded Prof. Vallier, Professor of Stem Cells in Regenerative Therapies at the Berlin Institute of Health at Charité (BIH).

Reference: SHOTA NAKANOH, KENDIG SHAM, SABITRI GHIMIRE, IRINA MOHORIANU, TERESA RAYON, LUDOVIC VALLIER; JOURNAL: Science Advances; DOI: 10.1126/sciadv.adh7748