Gene expression profile of cells with unfit Wnt morphogen gradient during cell competition
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PROVIDER: PRJNA551686 | ENA |
REPOSITORIES: ENA
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Project description:Morphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradient. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signalling gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, revealed that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.
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Project description:This model couples BMP morphogen gradient formation with Smad signaling in zebrafish and reproduces Fig.3B of the referenced paper. mBMP4 diffuses and forms a morphogen gradient in the host tissue where differential signal transduction kinetics for pSmad2 versus pSmad5 lead to narrow (pSmad2) versus wide (pSmad5) signal activity ranges in response to the same morphogen gradient (mBMP4) as input. The model file is in MorpheusML format and can be opened in the free, open-source multicellular modeling software Morpheus (https://morpheus.gitlab.io) to simulate the time course (movie) of the spatio-temporal dynamics. Further optional plots of the radial solution profile and the time courses of mean concentrations over the domain are included and temporarily inactivated in the model file, in section Analysis.
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Project description:To investigate miRNAs that implicate the process of adipogenesis by interacting with canonical Wnt/β-catenin signaling pathway, we constructed two cell models at first, and then investigated the expression profile of microRNAs by using Microarray. Based on the data of high throughput microarray, we identified 18 miRNAs which might promote adipogenesis by repressing WNT signaling, including mir-210, mir-148a, mir-194, mir-322 etc. On the other hand, we also identified 29 miRNAs which might repress adipogenesis by activation of WNT signaling, including mir-344, mir-27, and mir-181. The target genes involved in WNT signaling pathway of these identified miRNAs were also predicted through online tools. Two cell models of 3T3-L1, i.e. activation and suppression of WNT signaling including four samples, i.e. preadipocytes, mature adipocytes (MDI induction), Lithium treated preadipocytes, MDI induction of Lithium treated preadipocytes. Each sample was replicated in triplicate.
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Project description:To investigate miRNAs that implicate the process of adipogenesis by interacting with canonical Wnt/β-catenin signaling pathway, we constructed two cell models at first, and then investigated the expression profile of microRNAs by using Microarray. Based on the data of high throughput microarray, we identified 18 miRNAs which might promote adipogenesis by repressing WNT signaling, including mir-210, mir-148a, mir-194, mir-322 etc. On the other hand, we also identified 29 miRNAs which might repress adipogenesis by activation of WNT signaling, including mir-344, mir-27, and mir-181. The target genes involved in WNT signaling pathway of these identified miRNAs were also predicted through online tools.
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Project description:In early neurodevelopment, the central nervous system is established through the coordination of various neural organizers directing tissue patterning and cell differentiation. Better recapitulation of morphogen gradient production and signaling will be crucial for establishing improved developmental models of the brainin vitro. Here, we developed a method by assembling polydimethylsiloxane (PDMS) devices capable of generating a sustained chemical gradient to produce patterned brain organoids, which we termedMorphogen-gradientInducedBrainOrganoids (MIBOs). At 3.5 weeks, MIBOs replicated Dorsal-Ventral patterning observed in the Ganglionic Eminence (GE). Analysis of matured MIBOs through single-cell RNA sequencing revealed distinct Dorsal GE derived CALB2+ interneurons (INs), Medium Spiny Neurons (MSNs), and MGE derived cell types. Finally, we demonstrate long term culturing capabilities with MIBOs maintaining stable neural activity in cultures grown up to 5.5 months. MIBOs demonstrate a versatile approach for generating spatially patterned brain organoids for embryonic development and disease modeling.
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