Similar Datasets
Project description:Understanding the interplay between cell fate specification and morphogenetic changes remains a central challenge in developmental biology. Gastruloids, self-organizing pseudo-embryos that mimic post-implantation mammalian development, provide a powerful platform to address this question. Here, we show that physical parameters, particularly system size, critically influence the timing and outcomes of morphogenetic processes. Larger gastruloids exhibit delayed symmetry breaking, increased multipolarity, and prolonged axial elongation, with morphogenesis driven by system size. Despite these variations, transcriptional programs and cell fate composition remain remarkably stable across a broad size range. Notably, extreme sizes show distinct transcriptional modules and clear shifts in gene expression patterns. Intriguingly, size perturbation experiments rescued the morphogenetic and pattern phenotypes observed in extreme sizes, demonstrating the remarkable adaptability of gastruloids to their effective system size. These findings establish gastruloids as versatile models for studying spatiotemporal dynamics in mammalian embryogenesis and reveal how physical constraints decouple transcriptional from morphogenetic programs.
2025-09-08 | GSE288157 | GEO
Project description:Understanding the interplay between cell fate specification and morphogenetic changes remains a central challenge in developmental biology. Gastruloids, self-organizing pseudo-embryos that mimic post-implantation mammalian development, provide a powerful platform to address this question. Here, we show that physical parameters, particularly system size, critically influence the timing and outcomes of morphogenetic processes. Larger gastruloids exhibit delayed symmetry breaking, increased multipolarity, and prolonged axial elongation, with morphogenesis driven by system size. Despite these variations, transcriptional programs and cell fate composition remain remarkably stable across a broad size range. Notably, extreme sizes show distinct transcriptional modules and clear shifts in gene expression patterns. Intriguingly, size perturbation experiments rescued the morphogenetic and pattern phenotypes observed in extreme sizes, demonstrating the remarkable adaptability of gastruloids to their effective system size. These findings establish gastruloids as versatile models for studying spatiotemporal dynamics in mammalian embryogenesis and reveal how physical constraints decouple transcriptional from morphogenetic programs.
2025-09-08 | GSE288155 | GEO
Project description:Fine-tuning mechanical constraints reveals uncoupled patterning and gene expression programs in murine gastruloids
| PRJNA1216289 | ENA
Project description:Fine-tuning mechanical constraints reveals uncoupled patterning and gene expression programs in murine gastruloids [RNAseq_time]
| PRJNA1216285 | ENA
Project description:Fine-tuning mechanical constraints reveals uncoupled patterning and gene expression programs in murine gastruloids [RNAseq_concentration]
| PRJNA1216293 | ENA
Project description:BMP signaling plays a crucial role in the establishment of the dorso-ventral body axis in bilaterally symmetric animals. However, the topologies of the bone morphogenetic protein (BMP) signaling networks vary drastically in different animal groups, raising questions about the evolutionary constraints and evolvability of BMP signaling systems. Using loss-of-function analysis and mathematical modeling, we show that two signaling centers expressing different BMPs and BMP antagonists maintain the secondary axis of the sea anemone Nematostella. We demonstrate that BMP signaling is required for asymmetric Hox gene expression and mesentery formation. Computational analysis reveals that network parameters related to BMP4 and Chordin are constrained both in Nematostella and Xenopus, while those describing the BMP signaling modulators can vary significantly. Notably, only chordin, but not bmp4 expression needs to be spatially restricted for robust signaling gradient formation. Our data provide an explanation of the evolvability of BMP signaling systems in axis formation throughout Eumetazoa.
| S-EPMC4460265 | biostudies-literature
Project description:Minimal in vitro systems composed of embryonic stem cells (ESCs) have been shown to recapitulate the establishment of the anteroposterior (AP) axis. In contrast to the native embryo, ESC aggregates - such as gastruloids - can break symmetry, which is demarcated by polarization of the mesodermal marker T, autonomously without any localized external cues. However, associated earliest patterning events, such as the spatial restriction of cell fates and concomitant transcriptional changes, remain poorly understood. Here, we dissect the dynamics of AP axis establishment in mouse gastruloids, particularly before external Wnt stimulation. Through single-cell RNA sequencing, we identify key cell state transitions and the molecular signatures of T+ and T- populations underpinning AP polarization. We also show that this process is robust to modifications of aggregate size. Finally, transcriptomic comparison with the mouse embryo indicates that gastruloids develop similar mesendodermal cell types, despite initial differences in their primed pluripotent populations, which adopt a more mesenchymal state in lieu of an epiblast-like transcriptome. Hence, our findings suggest the possibility of alternate ESC states in vivo and in vitro that can converge onto similar cell fates.
| S-EPMC11607688 | biostudies-literature
Project description:The gastrulation process relies on complex interactions between developmental signaling pathways that are not completely understood. Here, we interrogated the contribution of the Hippo signaling effector YAP1 to the formation of the three germ layers by analyzing human embryonic stem cell (hESC)-derived 2D-micropatterned gastruloids. YAP1 knockout gastruloids display a reduced ectoderm layer and enlarged mesoderm and endoderm layers compared with wild type. Furthermore, our epigenome and transcriptome analysis revealed that YAP1 attenuates Nodal signaling by directly repressing the chromatin accessibility and transcription of key genes in the Nodal pathway, including the NODAL and FOXH1 genes. Hence, in the absence of YAP1, hyperactive Nodal signaling retains SMAD2/3 in the nuclei, impeding ectoderm differentiation of hESCs. Thus, our work revealed that YAP1 is a master regulator of Nodal signaling, essential for instructing germ layer fate patterning in human gastruloids.
| S-EPMC8828531 | biostudies-literature
Project description:The role of FGF is the least understood of the morphogens driving mammalian gastrulation. Here we investigated the function of FGF in a stem cell model for human gastrulation known as a 2D gastruloid. We found a ring of FGF-dependent ERK activity that closely follows the emergence of primitive streak (PS)-like cells but expands further inward. We showed that this ERK activity pattern is required for PS-like differentiation and that loss of PS-like cells upon FGF receptor inhibition can be rescued by directly activating ERK. We further demonstrated that the ERK-ring depends on localized activation of basally localized FGF receptors (FGFR) by endogenous FGF gradients. We confirm and extend previous studies in analyzing expression of FGF pathway components, showing the main receptor to be FGFR1 and the key ligands FGF2/4/17, similar to the human and monkey embryo but different from the mouse. In situ hybridization and scRNA-seq revealed that FGF4 and FGF17 expression colocalize with the PS marker TBXT but only FGF17 is maintained in nascent mesoderm and endoderm. FGF4 and FGF17 reduction both reduced ERK activity and differentiation to PS-like cells and their derivatives, indicating overlapping function. Thus, we have identified a previously unknown role for FGF-dependent ERK signaling in 2D gastruloids and possibly the human embryo, driven by a mechanism where FGF4 and FGF17 signal through basally localized FGFR1 to induce PS-like cells.
| S-EPMC11257619 | biostudies-literature
Project description:Although the importance of undergraduate research experiences in preparing students for graduate study and research careers is well documented, specific examination of program components is needed to assess the impact of these programs on underrepresented (UR) students. The Leadership Alliance, a consortium of leading PhD-granting and minority-serving institutions (MSIs), has leveraged its diverse partnership to place UR students from MSI and non-MSI institutions in competitive research environments through its national Summer Research Early Identification Program. Using longitudinal pre/post data collected from student surveys, we applied social cognitive career theory as a conceptual framework to examine how research engagement, skill development, and mentorship aspects of a summer research program affect students' commitment to pursue research careers. Self-reported knowledge of research skills, time engaged in research activity, and students' understanding of and attitudes toward pursuing graduate study were measured in relation to the classification of students' home undergraduate institution, level of students' pre-existing research experience, and demographic factors. Our results provide evidence of specific programmatic components that are beneficial for UR students from varying academic and cultural backgrounds. This study describes important aspects of summer research programs that will contribute to students' ability to persist in science careers.
| S-EPMC5008875 | biostudies-literature