Biology subjects

Liu, Y.

Publications and source records attributed to Liu, Y..

At least 1,405 records · Page 78Linked to original sources

bioRxiv2023

Mutation Impact on mRNA Versus Protein Expression across Human Cancers

Cancer mutations are often assumed to alter proteins, thus promoting tumorigenesis. However, how mutations affect protein expression has rarely been systematically investigated. We conduct a comprehensive analysis of mutation impacts on mRNA- and protein-level expressions of 953 cancer cases with paired genomics and global proteomic profiling across six cancer types. Protein-level impacts are validated for 47.2% of the somatic expression quantitative trait loci (seQTLs), including mutations from likely "long-tail" driver genes. Devising a statistical pipeline for identifying somatic protein-specific QTLs (spsQTLs), we reveal several gene mutations, including NF1 and MAP2K4 truncations and TP53 missenses showing disproportional influence on protein abundance not readily explained by transcriptomics. Cross-validating with data from massively parallel assays of variant effects (MAVE), TP53 missenses associated with high tumor TP53 proteins were experimentally confirmed as functional. Our study demonstrates the importance of considering protein-level expression to validate mutation impacts and identify functional genes and mutations.

genomics↗

bioRxiv2023

Olfaction foraging in visually oriented tropical arboreal ants Oecophylla smaragdina: Implications for insect predation studies using artificial sentinel prey

Predation is the key to understanding trophic interactions. Because of the brief and cryptic nature of predatory behavior, sentinel prey has been widely adopted as an indirect way to identify predators and understand trophic interactions. However, sentinel prey presents only static visual cues, potentially biasing toward visually oriented predators whilst ignoring those that require other sensory cues to forage. Despite this, the effectiveness of sentinel prey has rarely been tested. Here, we focused on the weaver ant, Oecophylla smaragdina, a keystone predator widespread in the Asian and Australian tropics. As this species has large eyes and is known to visually navigate in their arboreal habitats, we hypothesized that they rely on visual cues to forage and that their predatory behavior will be captured by caterpillar-shaped sentinel prey. Ants were collected as colonies, and preference trials on baits were conducted using combinations of olfactory and static visual cues including the caterpillar shape. Surprisingly, O. smaragdina showed little or no preference for baits in the absence of olfactory cues and did not differentiate the shapes of baits regardless of the presence of olfactory cues. Our results indicate that O. smaragdina is likely to make predatory decisions based primarily on olfactory cues, while visual cues might be used for other behaviors. Furthermore, O. smaragdina is likely to be left out by the predation studies using sentinel prey models which is particularly alarming considering the dominant role of this species in the trophic interactions of tropical rainforests. Our study demonstrates that morphological characteristics, arboreal habitats, and visually oriented behavior do not necessarily suggest the use of static visual cues for predatory decisions. We suggest that sentinel prey models should not be used alone when the dominant predators are unlikely to use visual cues to make predatory decisions.

ecology↗

bioRxiv2023

Abnormal white matter development during early childhood in autism and developmental disability

The abnormal maturation of white matter microstructure in autism spectrum disorder (ASD) compared with typical developing (TD) and developmental delay/intellectual disorder (DD/ID) during early childhood and their associations with clinical implications remain unclear. Here, we characterized spatial and temporal patterns of white matter development in 364 children (including ASD, DD/ID and TD) under 8 years old using neurite orientation dispersion and density imaging. Using neurite density index (NDI), we consistently detected three white matter clusters across all the groups through clustering analysis, indicating the conserved spatial layout in atypical development. Further, three developmental stages with successively lower growth rates were identified in ASD, similar to those in TD but delayed overall. Meanwhile, DD/ID children showed the slowest growth rates and lacked staging features. Finally, for ASD children, the NDI was correlated with cognitive impairments at the fast developmental stage but associated with social deficits during the moderate-to-slow stage.

neuroscience↗

bioRxiv2023

Lipid metabolism drives allele-specific early-stage hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) results from pathogenic variants in sarcomeric protein genes, that increase myocyte energy demand and lead to cardiac hypertrophy. But it is unknown whether a common metabolic trait underlies the cardiac phenotype at early disease stage. This study characterized two HCM mouse models (R92W-TnT, R403Q-MyHC) that demonstrate differences in mitochondrial function at early disease stage. Using a combination of cardiac phenotyping, transcriptomics, mass spectrometry-based metabolomics and computational modeling, we discovered allele-specific differences in cardiac structure/function and metabolic changes. TnT-mutant hearts had impaired energy substrate metabolism and increased phospholipid remodeling compared to MyHC-mutants. TnT-mutants showed increased incorporation of saturated fatty acid residues into ceramides, cardiolipin, and increased lipid peroxidation, that could underlie allele-specific differences in mitochondrial function and cardiomyopathy. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=172 HEIGHT=200 SRC="FIGDIR/small/564562v1_ufig1.gif" ALT="Figure 1"> O_LINKSMALLFIG WIDTH=185 HEIGHT=200 SRC="FIGDIR/small/564562v1_ufig2.gif" ALT="Figure 1"> O_LINKSMALLFIG WIDTH=200 HEIGHT=74 SRC="FIGDIR/small/564562v1_ufig3.gif" ALT="Figure 1"> View larger version (90K): org.highwire.dtl.DTLVardef@195b1d7org.highwire.dtl.DTLVardef@cead88org.highwire.dtl.DTLVardef@e2bf35org.highwire.dtl.DTLVardef@776765_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2023

Paternal genomic resources from the YanHuang cohort suggested a Weakly-Differentiated Multi-source Admixture model for the formation of Hans founding ancestral lineages

The large-scale human genome revolution and rapidly advanced statistical innovation have updated our understanding of the fine-scale and complex genetic structure, the entire landscape of genetic diversity and the evolutionary trajectories of spatiotemporally different ancients and ethnolinguistically diverse modern populations. Recent ancient DNA research provided a detailed and complex admixture picture of ancient Europeans but limited insights into East Asians as the few available genomes. Y-chromosome variations in the male-specific regions, served as molecular archaeological tool, have unique evolutionary features that can be utilized to reconstruct the origin and subsequent interaction of ancient East Asian paternal lineages. We launched the YanHuang cohort using our designed highest-resolution capture sequencing panel to explore the detailed evolutionary trajectory of the Han Chinese, one of the largest ethnic groups in the world. We reported one of the largest uniparental genomic resources and observed multiple founding paternal lineages dominant in ancient western Eurasian, Siberian and East Asian participating in the formation of the gene pool of the Han Chinese. We identified fine-scale paternal genetic structure correlated with different patterns of ancient population interaction and geographical mountain barriers (Qinling-Huaihe line and Nanling Mountains), suggesting isolation-enhanced and admixture-introduced genetic differentiation enhanced the complexity of the Han Chinese genomic diversity. We observed a strong direct correlation between the frequency of multiple founding lineages of the Han Chinese and the proportion of subsistence-related ancestry sources related to western pastoralists, Holocene Mongolian Plateau people and ancient East Asians, reflecting the ancient migration events contributed to our identified patterns of Chinese paternal genomic diversity. We finally provided one novel and the most plausible admixture-by-admixture model, the Weakly-Differentiated Multi-Source Admixture model, as the major genetic mechanism to illuminate our observed pattern of complex interactions of multiple ancestral sources and landscape of the Han Chinese paternal genetic diversity. Generally, we presented one large-scale uniparental genomic resource from the YanHuang cohort, portrayed one novel admixture formation model and presented the entire genomic landscape with multiple ancestral sources related to ancient herders, hunter-gatherers and farmers who participated in the ancestral formation of the Han Chinese.

evolutionary biology↗

bioRxiv2023

The change of lymphocyte subsets and inflammatory cytokine in BK viruria

BackgroundPolyomavirus BK (BKV) infection as a serious complication after kidney transplantation. The process of infections in kidney transplant recipients is viruria, viremia, and BKVAN. The difference between BK negative and BK viruria in kidney recipients has not been defined. Patients and MethodsWe compared post-transplant lymphocyte subsets blood cytokinesurine cytokines levels of 19 renal transplant outpatients with (BK-positive) or without BK viruria (BK-negative, n=20), and 20 healthy controls (HCs). Group of BK-positive divide into low-(n=4) and high-level (n=15) According to BK viral load (VL).Immune cells including T cells, B cells, and natural killer (NK) cellsinterleukin-2(IL-2),IL-5,IL-6, IL-1{beta}, IL-10, IL-8, IL-17A,IL-4,IL-12P70, interferon-(IFN-), IFN-{gamma},and tumor necrosis factor- (TNF-)were determined by flow cytometry. ResultsBK-positive patients showed higher urine IL-1{beta} (P=0.040), IL-10 (P= 0.010), IFN-{gamma} (P =0.002), and TNF- (P =0.027) than BK-negative patients. Compared with HCs, BK-negative patients had lower urine IL-1{beta} (P=0.04), IL-10 (P=0.01), TNF- (P =0.027) and IFN-{gamma} (P =0.004),suggesting that cytokine expression regulation BK-infection. ConclusionBK-positive renal transplant recipients, especially those with high VL, showed strong inflammatory cytokine responses with increases of urine IL-1{beta}, IL-10, IFN-{gamma}, and TNF-. Our data suggest that monocyte- and Th-2-induced cytokines are involved in the pathogenesis of BKV-associated nephropathy.

immunology↗

bioRxiv2023

Structure of scavenger receptor SCARF1 and its interaction with lipoproteins

SCARF1 (Scavenger receptor class F member 1, SREC-1 or SR-F1) is a type I transmembrane protein that recognizes multiple endogenous and exogenous ligands such as modified low-density lipoproteins (LDL) and is important for maintaining homeostasis and immunity. But the structural information and the mechanisms of ligand recognition of SCARF1 are largely unavailable. Here we solve the crystal structures of the N-terminal fragments of human SCARF1, which show that SCARF1 forms homodimers and its epidermal growth factor (EGF)-like domains adopt a long-curved conformation. Then we examine the interactions of SCARF1 with lipoproteins and are able to identify a region on SCARF1 for recognizing modified LDLs. The mutagenesis data show that the positively charged residues in the region are crucial for the interaction of SCARF1 with modified LDLs, which is confirmed by making chimeric molecules of SCARF1 and SCARF2. In addition, teichoic acids, a cell wall polymer expressed on the surface of gram-positive bacteria, are able to inhibit the interactions of modified LDLs with SCARF1, suggesting the ligand binding sites of SCARF1 might be shared for some of its scavenging targets. Overall, these results provide mechanistic insights into SCARF1 and its interactions with the ligands, which are important for understanding its physiological roles in homeostasis and the related diseases.

biophysics↗

bioRxiv2023

MiRGraph: A transformer-based feature learning approach to identify miRNA-target interactions

MicroRNAs (miRNAs) mediates gene expression regulation by targeting specific messenger RNAs (mRNAs) in the cytoplasm. They can function as both tumor suppressors and oncogenes depending on the specific miRNA and its target genes. Detecting miRNA-target interactions (MTIs) is critical for unraveling the complex mechanisms of gene regulation and promising towards RNA therapy for cancer. There is currently a lack of MTIs prediction methods that simultaneously perform feature learning from heterogeneous gene regulatory network (GRN) and genomic sequences. To improve the prediction performance of MTIs, we present a novel transformer-based multiview feature learning method - MiRGraph, which consists of two main modules for learning the sequence-based and GRN-based feature embedding. For the former, we utilize the mature miRNA sequences and the complete 3UTR sequence of the target mRNAs to encode sequence features using a hybrid transformer and convolutional neural network (CNN) (TransCNN) architecture. For the latter, we utilize a heterogeneous graph transformer (HGT) module to extract the relational and structural information from the GRN consisting of miRNA-miRNA, gene-gene and miRNA-target interactions. The TransCNN and HGT modules can be learned end-to-end to predict experimentally validated MTIs from MiRTarBase. MiRGraph outperforms existing methods in not only recapitulating the true MTIs but also in predicting strength of the MTIs based on the in-vitro measurements of miRNA transfections. In a case study on breast cancer, we identified plausible target genes of an oncomir.

bioinformatics↗

bioRxiv2023

DeepVASP-S: a deep-learning tool for explaining steric mechanism that controls binding specificity

DeepVASP-S is a computational tool that leverages the capabilities of convolutional neural networks (CNNs) to analyze steric aspects of protein-ligand interactions and predict amino acid contributions to binding specificity. This tool combines structural bioinformatics with machine learning to address the complex problem of understanding how specific amino acids contribute to the specificity of binding. Here, we use this tool to predict subclasses for Enolase and Serine Protease according to their binding specificity, and explain it through the underlying steric mechanism. The strength of DeepVASP-S lies in its ability to identify and highlight these specific regions, providing researchers with insights into the molecular determinants of protein function and interaction. Such information is extremely valuable for the field of drug design, as it enables the creation of more targeted and effective therapeutics with minimized side effects. The approach taken by DeepVASP-S represents a significant step forward in computational biochemistry, merging high-resolution 3D structural data with the predictive power of machine learning to unlock a deeper understanding of protein-ligand interactions.

bioinformatics↗

bioRxiv2023

One infusion of engineered long-lasting and multifunctional T cells cures asthma in mice

The majority of common chronic human diseases are incurable, which affect a large portion of population and require life-long treatments that impose huge disease, economic and social burden. For example, asthma is the most common respiratory disease affecting over 300 million people and accounts for > 250,000 death annually, for which there is no cure. Unlike traditional therapyies, engineered T cells, such as chimeric antigen receptor CAR T (CAR-T) cells, function as living drugs and can cure some hematological malignancies, but whether engineered T cells can cure common diseases beyond cancer remains elusive. Here, we develop a curative therapy for asthma based on enginerred T cell. With IL-5 as the targeting domain and depletion of BCOR and ZC3H12A, we produce long-lasting CAR-T cells eradicating IL-5R+ eosinophils, termed Immortal-like and Functional IL-5 CAR-T cells (5TIF) cells. We further enginerred 5TIF cells to secrete an IL-4 mutein that blocks the singaling of both IL-4 and IL-13, two driver inflammatory cytokines in asthma, named as 5TIF4 cells. In multiple models of asthma, one infusion of 5TIF4 cells in fully immunocompetent mice, in the absence of any conditioning regimen, confers long-term depletion of pathological eosinophils and blockade of IL-4/IL-13 actions, resulting in sustained repression of type 2 inflammation and asthmatic symptoms. Furthurmore, 5TIF4 cells can also be induced in human T cells in NSG mice. Our data demonstrate that asthma, a common noncancerous disease, can be cured by a single infusion of engineered long-lasting and multifunctional T cells, which paves the way for curing common chronic diseases by engineered long-lived T cells.

immunology↗

bioRxiv2023

Induction of immortal-like and functional CAR-T cells by defined factors

Long-term antitumor efficacy of chimeric antigen receptor (CAR)-T cells depends on their functional persistence in vivo. T cells with stem-like property show better persistence, but factors conferring T cells bona fide stemness remain to be determined. Here, we demonstrate the induction of CAR-T cells into an immortal-like and functional state, termed TIF. The induction of CAR-TIF cells depends on repression of two factors: BCOR and ZC3H12A, and requires antigen or CAR tonic signaling. The reprogrammed CAR-TIF cells possess almost infinite stemness resembling induced pluripotent stem cells but retain functionality of mature T cells, which exhibit superior antitumor effect. CAR-TIF cells enter a metabolically dormant state after elimination of target cells, which persist in vivo with a saturable niche and mediate memory protection. CAR-TIF cells represent a novel state of T cells with unprecedented stemness conferring long-term functional persistence of CAR-T cells in vivo, which have broad potentials in T cell therapies.

immunology↗

bioRxiv2023

Single cell RNA-seq reveals protracted germ line X chromosome reactivation dynamics directed by a PRC2 dependent mechanism

Initiating soon after PGC specification, female germ cells undergo reactivation of the silenced X chromosome during genome wide reprogramming. However, the kinetics and dynamics of XCR in vivo have remained poorly understood. To address this here we perform a global appraisal of XCR using high-dimensional techniques. Using F1 B6 v CAST mouse embryos, we perform a detailed assessment, applying single-cell RNA-seq and chromatin profiling on germ cells purified from E10.5 to E16.5. While scRNA-seq profile showed that male and female germ cells are transcriptionally indistinct at E11.5, they are sexually dimorphic by E12.5, diverging further through development to E16.5. With allelic resolution, we show that the reactivating X chromosome is only partly active at E10.5, then reactivates gradually and reaches near parity in output to the constitutively active X chromosome at [~]E16.5 when developing oogonia are meiosis prophase I. Crucially, we show that sexually dimorphic dosage compensation patterns observed in germ cells, occur in tandem with an increase in the allelic proportion from the reactivating X chromosome. While Xist is extinguished from E10.5, the epigenetic memory of earlier XCI in female cells persists much longer, likely from self-sustained PRC2 complex (Ezh2 / Eed / Suz12) function. The reactivating X chromosome is enriched in the epigenetic silencing mark H3K27me3 at E13.5, which is removed by E16.5 permitting gene expression. Our findings link XCR, along with functional regulation of PRC2 in promoting female meiosis.

developmental biology↗

bioRxiv2023

Stomatal maturomics: identifying genes regulating guard cell maturation and function formation from single-cell transcriptomes

Stomata play critical roles in gas exchange and immunity to pathogens. While many genes regulating early stomatal development up to the production of young guard cells (GCs) have been described in Arabidopsis, much less is known about how young GCs develop into mature functional stomata. Here we performed a maturomics study on stomata, with "maturomics" defined as omics analysis of the maturation process of a tissue or organ. We developed an integrative scheme to analyze three public stomata-related single-cell RNA-seq datasets and identified a list of 586 genes that were specifically up-regulated in all three datasets during stomata maturation and function formation. The list, termed sc_586, is enriched with known regulators of stomatal maturation and functions. We selected two candidate G2-like TFs genes, MYS1 and MYS2, from the list to investigate their roles in stomata. Our results showed that these two genes redundantly regulate the size and hoop rigidity of mature GCs, and their double mutations caused mature GCs to have severe defects in regulating their stomatal apertures. Our analysis thus provides a valuable gene list for studying GC maturation and function formation.

plant biology↗

bioRxiv2023

Crossroads of assembling a moss genome: navigating contaminants and horizontal gene transfer in the moss Physcomitrellopsis africana

The first chromosome-scale reference genome of the rare narrow-endemic African moss Physcomitrellopsis africana is presented here. Assembled from 73x nanopore long reads and 163x BGI-seq short reads, the 414 Mb reference comprises 26 chromosomes and 22,925 protein-coding genes (BUSCO: C:94.8%[D:13.9%]). This genome holds two genes that withstood rigorous filtration of microbial contaminants, have no homolog in other land plants and are thus interpreted as resulting from two unique horizontal gene transfers from microbes. Further, Physcomitrellopsis africana shares 176 of the 273 published HGT candidates identified in Physcomitrium patens, but lacks 98 of these, highlighting that perhaps as many as 91 genes were acquired in P. patens in the last 40 million years following its divergence from its common ancestor with P. africana. These observations suggest rather continuous gene gains via HGT followed by potential losses, during the diversification of the Funariaceae. Our findings showcase both dynamic flux in plant HGTs over evolutionarily "short" timescales, alongside enduring impacts of successful integrations, like those still functionally maintained in extant Physcomitrellopsis africana. Furthermore, this study describes the informatic processes employed to distinguish contaminants from candidate HGT events. Article SummaryThe first draft genome of the rare South African endemic moss Physcomitrellopsis Africana is presented. The 414 Mb assembly contains 22,925 genes, including two uniquely horizontally transferred genes, but lacks 97 of the microbial genes previously identified in the closely related model, Physcomitrium patens - highlighting the dynamic role of HGT in the evolution of these moss genomes and loss. This study presents best practices for contamination detection and new insights into HGT identification.

genomics↗

bioRxiv2023

Polygonum Cillinerve polysaccharide inhibits Transmissible gastroenteritis virus by regulating microRNA-181

Transmissible gastroenteritis virus (TGEV) is an important pathogen that can cause changes in the expression profile of cell miRNA. In this study, PCP could treat piglets infected with TGEV by in vivo experiment. High-throughput sequencing technology was used to detect that 9 miRNAs were up-regulated and 17 miRNAs were down-regulated during PCP inhibition of TGEV infection in PK15 cells. Meanwhile, miR-181 was related to the target genes of key proteins of apoptosis pathway. PK15 was treated with different PCP after transfection of miR-181 mimic or inhibitor. Real-time PCR was used to detect the effect of TGEV replication, electron microscopy, TEM and Hoechst fluorescence staining were used to detect the biological function of the treated cells, and western blot (WB) was used to detect the expression of key signaling factors cyt C, caspase 9 and P53 in the apoptotic signaling pathway. The results showed that compared with the control group, 250 g/mL PCP significantly inhibited the replication of TGEV gRNA and gene N (P < 0.01). PK15 cells in PCP groups (250 and 125 g/mL) had uniform cell morphology and a small number of floating cells by microscopic, no typical virus structure was observed in 250 g/mL PCP group under TEM, and apoptosis staining showed that 250 g/mL PCP significantly reduced the number of apoptotic cells. PCP may inhibit TGEV-induced apoptosis through Caspase-dependent mitochondrial pathway after transfection of miR-181. The above results provided a theoretical basis for further research on the mechanism of PCP anti-TGEV.

pharmacology and toxicology↗

bioRxiv2023

Development of Corynebacterium glutamicum as a monoterpene production platform

Monoterpenes are commonly known for their role in the flavors and fragrances industry and are also gaining attention for other uses like insect repellant and as potential renewable fuels for aviation. Corynebacterium glutamicum, a Generally Recognized as Safe microbe, has been a choice organism in industry for the annual million ton-scale bioproduction of amino acids for more than 50 years; however, efforts to produce monoterpenes in C. glutamicum have remained relatively limited. In this study, we report a further expansion of the C. glutamicum biosynthetic repertoire through the development and optimization of a mevalonate-based monoterpene platform. In the course of our plasmid design iterations, we increased flux through the mevalonate-based bypass pathway, measuring isoprenol production as a proxy for monoterpene precursor abundance and demonstrating the highest reported titers in C. glutamicum to date at nearly 1500 mg/L. Our designs also evaluated the effects of backbone, promoter, and GPP synthase homolog origin on monoterpene product titers. Monoterpene production was further improved by disrupting competing pathways for isoprenoid precursor supply and by implementing a biphasic production system to prevent volatilization. With this platform, we achieved 321.1 mg/L of geranoids, 723.6 mg/L of 1,8-cineole, and 227.8 mg/L of linalool. Furthermore, we determined that C. glutamicum first oxidizes geraniol through an aldehyde intermediate before it is asymmetrically reduced to citronellol. Additionally, we demonstrate that the aldehyde reductase, AdhC, possesses additional substrate promiscuity for acyclic monoterpene aldehydes. HighlightsO_LIDesign of a mevalonate-based monoterpene production platform in C. glutamicum C_LIO_LIHighest production titers of geranoids, eucalyptol, and linalool reported in C. glutamicum to date C_LIO_LIIdentification of citronellal as an intermediate in the reduction of geraniol to citronellol by C. glutamicum C_LI

synthetic biology↗

bioRxiv2023

Modern wheat breeding selection synergistically improves above- and below-ground traits

The root system, as a fundamental organ for uptaking water and nutrients and interacting with the local environmental conditions, has been postulated to be the foundation for a second Green Revolution. However, the status of the root system during modern wheat breeding remains to be elucidated. Here, by analyzing the phenotypes of 406 wheat accessions on a large scale, we found the root systems of modern cultivars were synchronisely changed along with the above-ground traits. Furthermore, the genomic blocks with phenotypic effects on both above- and below-ground traits were observed to be enriched in the selection sweeps, highlighting that modern wheat breeding contributed to the synchronised changes. More importantly, the haplotypes selected by breeders within the selection sweeps synergistically improved both the above- and below-ground traits, suggesting that modern wheat breeding has improved the root system indirectly, which may contribute to the higher grain yields of modern wheat cultivars. Our results demonstrated that modern wheat breeding synergistically improved the above- and below-ground traits.

genetics↗

bioRxiv2023

A human pluripotent stem cell-based somitogenesis model using microfluidics

Emerging human pluripotent stem cell (hPSC)-based embryo models are useful for studying human embryogenesis. Particularly, there are hPSC-based somitogenesis models using free-floating culture that recapitulate somite formation. Somitogenesis in vivo involves intricately orchestrated bio-chemical and -mechanical events. However, none of the current somitogenesis models controls biochemical gradients or biomechanical signals in the culture, limiting their applicability to untangle complex biochemical-biomechanical interactions that drive somitogenesis. Here we report a new human somitogenesis model by confining hPSC-derived presomitic mesoderm (PSM) tissues in microfabricated trenches. Exogenous microfluidic morphogen gradients imposed on PSM cause axial patterning and trigger spontaneous rostral-to-caudal somite formation. A mechanical theory is developed to explain the size dependency between somites and PSM. The microfluidic somitogenesis model is further exploited to reveal regulatory roles of cellular and tissue biomechanics in somite formation. This study presents a useful microengineered, hPSC-based model for understanding the bio-chemical and -mechanical events that guide somite formation.

bioengineering↗