Core Insights - The research conducted by Tsinghua University's team addresses the "WNT signaling gradient paradox" in gastric development, which has puzzled the academic community for 20 years [1][2][3] - The study introduces a novel gastric organoid model that simulates early human gastric development, providing new pathways for organ development research and translational medicine applications [1][5] Summary by Sections WNT Signaling Gradient Paradox - The "WNT signaling gradient paradox" refers to the contradictory findings regarding the WNT signaling gradient in gastric organ development, where traditional theories suggest a gradient increase from anterior to posterior, while gastric development actually requires a decreasing gradient [2][3] - WNT proteins are crucial signaling molecules that guide embryonic development by instructing cells on tissue formation and positioning [2] Discovery of the Gastric Organoid Model - The research team proposed that the decreasing WNT signaling gradient is generated by an undiscovered "dark matter signal source," which acts as a dedicated WNT signaling regulatory center for gastric development [4] - A three-dimensional culture system was developed to accurately replicate the extracellular matrix and mechanical stimuli present during embryonic development, allowing for the successful induction of a gastric organoid model named "gastric organoid" [4][5] Mechanism of Asymmetric Gastric Development - The gastric organoid model demonstrated that the neural tissue serves as a specialized signaling center, creating a high concentration of WNT signals in the anterior region, which decreases towards the posterior, thus fulfilling the requirements for gastric development [5][6] - The study identified the epithelial transcription factor NR2F2 as a key factor in determining the asymmetric pattern of gastric tissue, revealing new mechanisms behind gastric developmental abnormalities [6][7] Theoretical and Practical Implications - The research reconstructs the signaling regulatory system of organ development, integrating neural tissue as a core regulatory component and challenging traditional single-cell lineage theories [7][8] - The gastric organoid model fills a significant gap in early human gastric development research, providing a tool for studying gastric diseases and drug development, as well as advancing the construction of artificial gastric organs [8]

Core Insights - The research team led by Dr. Bai Bing from Kunming University of Science and Technology has collaborated with domestic and international researchers to resolve the "WNT signal gradient paradox" that has troubled developmental biology for 20 years, and has created an in vitro model of a gastric organoid that includes both the fundus and antrum regions, providing a new research platform for understanding human gastric organ development [1][2] Group 1 - The gastric organ, as a crucial digestive organ, has its functional regions, the fundus and antrum, formed as early as the 5th week of embryonic development [1] - The classical theory of developmental biology posits that organ patterning along the anterior-posterior axis relies on an increasing WNT signal gradient, while gastric development exhibits a decreasing WNT signal distribution, leading to the identified paradox [1] - The research team proposed the "hidden signaling center" hypothesis, suggesting the existence of undiscovered WNT signaling regulatory sources in gastric development [1][2] Group 2 - Through bioinformatics analysis, the team identified neural tissue as a key breakthrough, constructing a three-dimensional culture system that simulates the in vivo environment [2] - The team successfully induced pluripotent stem cells to develop a gastric organoid model with a bipolar distribution of fundus and antrum, which closely resembles the early human gastric organ at the molecular, cellular, and tissue structural levels [2] - The model visually demonstrates the asymmetric development process of the gastric anterior-posterior axis for the first time [2] Group 3 - Experimental validation confirmed that neural tissue, through its asymmetric geometric relationship with gastric epithelial tissue, forms a decreasing WNT signal gradient along the anterior-posterior axis, acting as a signaling center for gastric region development [2] - The epithelial-derived NR2F2 gene was identified as a critical regulatory factor for gastric tissue patterning, with its absence leading to an imbalance in fundus-antrum development, providing new insights into the mechanisms of gastric diseases [2] - This research enhances the classical signaling center theory in developmental biology and establishes the first in vitro research platform that simulates early human gastric organ development, addressing ethical limitations related to the scarcity of human embryonic samples [2]

Core Viewpoint - The research presents a new model of human gastric organoids, termed "gastroids," which successfully replicates the asymmetric tissue patterning along the anterior-posterior axis during early stomach development, addressing the WNT "signal gradient paradox" in gastric development [4][5][6]. Group 1 - The study was conducted by a collaborative team from Tsinghua University, Kunming University of Science and Technology, and other institutions, and published in the journal Nature [3]. - The gastroids developed from human pluripotent stem cells (hPSCs) exhibit a dual gastric fundus-antrum pattern and closely resemble in vivo gastric development at molecular, cellular, structural, and anatomical levels [5][6]. - The research identifies NR2F2 as a key factor mediating the formation of the gastric fundus-antrum pattern during the development of gastric organoids [5]. Group 2 - The study provides a unified new theory to resolve the existing paradox regarding the WNT signaling gradient in gastric organ development, which has challenged traditional developmental biology paradigms [5][6]. - The gastroids serve as a more realistic experimental platform for advancing research on gastric organogenesis and the development of gastric organoids [4][6].