Biology subjects

Eto, H.

Publications and source records attributed to Eto, H..

3 recordsLinked to original sources

bioRxiv2025

Human embryo implantation involves Syncytin-2/MFSD2A-mediated heterokaryon formation with maternal endometrium

Human embryo implantation involves attachment of the blastocyst to the endometrial epithelium to subsequently gain access to the underlying stromal compartment. The blastocyst is believed to cross the epithelium either by migration through, or upon apoptosis of, the endometrial epithelial cell layer. Yet, how the blastocyst exactly traverses the endometrial epithelium remains unknown. Here, we describe an in vitro implantation model of human blastoids and hormonally matured endometrial organoids amenable to high-resolution live imaging. We demonstrate that the initial step of implantation is mediated by the direct fusion of blastoid cells with endometrial epithelial cells. Blastoids express the fusion proteins Syncytin-1 and -2, while the endometrial epithelium mainly expresses the fusion co-receptor for Syncytin-2, called MFSD2A. CRISPR-induced loss of MFSD2A in the endometrial epithelium prevents blastoids from attaching and abolishes fusion. Together, these findings support a model in which fetal-maternal cell fusion constitutes the critical initiating mechanism of human embryo implantation, with endometrial MFSD2A playing an indispensable role in this process.

developmental biology↗

bioRxiv2024

NOTCH-driven oscillations control cell fate decisions during intestinal homeostasis

Intestinal homeostasis requires tight regulation of stem cell maintenance and commitment to absorptive and secretory cells, two key intestinal lineages1,2. While major signalling pathways critical for this control have been identified3, how they achieve such a tight balance in cell type composition remains unclear. Here, we uncover dynamic expression of Hes1, a direct NOTCH target3, in intestinal stem and progenitor cells, and investigate its role in vivo and in vitro. A knock-in reporter4 reveals distinct, cell-specific period lengths in Hes1 oscillations that form a gradient along the crypt-villus axis. Whereas secretory precursors oscillate at low periods, absorptive precursors oscillate at higher periods before transitioning to a differentiated state. To test the function of different oscillation periods, we innovated a microfluidic system that modulates Hes1 oscillations in organoids. We find that varying the oscillation period modulates secretory cell differentiation: While 90-min oscillations promote Paneth cells, 130-min oscillations increase formation of other secretory subtypes. Moreover, low-period oscillations support stemness and a proliferative state. Our study provides the first clear evidence that information for tissue homeostasis in the intestine is encoded in the temporal dynamics of signalling components.

cell biology↗

bioRxiv2019

The Polycomb group protein Ring1 regulates dorsoventral patterning of the mouse telencephalon

Patterning of the dorsal-ventral (D-V) axis of the mammalian telencephalon is fundamental to the formation of distinct functional regions including the neocortex and ganglionic eminences. Morphogenetic signaling by bone morphogenetic protein (BMP), Wnt, Sonic hedgehog (Shh), and fibroblast growth factor (FGF) pathways determines regional identity along this axis. It has remained unclear, however, how region-specific expression patterns of these morphogens along the D-V axis are established, especially at the level of epigenetic (chromatin) regulation. Here we show that epigenetic regulation by Ring1, an essential Polycomb group (PcG) protein, plays a key role in formation of ventral identity in the mouse telencephalon. Deletion of the Ring1b or both Ring1a and Ring1b genes in neuroepithelial cells of the mouse embryo attenuated expression of the gene for Shh, a key morphogen for induction of ventral identity, and induced misexpression of dorsal marker genes including those for BMP and Wnt ligands in the ventral telencephalon. PcG protein-mediated trimethylation of histone H3 on lysine-27 (H3K27me3) was also apparent at BMP and Wnt ligand genes in wild-type embryos. Importantly, forced activation of Wnt or BMP signaling repressed the expression of Shh in organotypic and dissociated cultures of the early-stage telencephalon. Our results thus indicate that epigenetic regulation by PcG proteins--and, in particular, that by Ring1-- confers a permissive state for the induction of Shh expression through suppression of BMP and Wnt signaling pathways, which in turn allows the development of ventral identity in the telencephalon.

developmental biology↗