Biology subjects

Guo, C.

Publications and source records attributed to Guo, C..

At least 109 records · Page 6Linked to original sources

bioRxiv2022

Species-dependent effects of seawater acidification on alkaline phosphatase activity in dinoflagellates

Global climate change is widely shown to cause ocean acidification (OA) and projected to intensify nutrient limitation. Phosphorus (P) is an essential nutrient for phytoplankton to grow. While dissolved inorganic phosphate (DIP) is the preferred form of P, phytoplankton have evolved alkaline phosphatase (AP) to utilize dissolved organic phosphorus (DOP) when DIP is deficient. Although AP is known to require pH>7, how OA may affect AP activity and hence the capacity of phytoplankton to utilize DOP is poorly understood. Here, we examine the effects of pH conditions (5.5 to 11) on AP activity from six species of dinoflagellates, an important group of marine phytoplankton. We observed a general pattern that AP activity declined sharply at pH 5.5, peaked between pH 7 and 8, and dropped at pH>8. However, our data revealed remarkable interspecific variations in optimal pH and niche breadth of pH. Among the species examined, Fugacium kawagutii and Prorocentrum cordatum had an optimal pH at 8, Alexandrium pacificum, Amphidinium carterae, Effrenium voratum, and Karenia mikimotoi showed an optimal pH of 7. However, whereas A. pacificum, F. kawagutii and K. mikimotoi had a broad pH range for AP (7-11), A. carterae, E. voratum, and P. cordatum exhibited a narrow pH range. The response of AP activity of A. carterae to pH changes was verified using purified AP heterologously expressed in Escherichia coli. These findings suggest that OA will likely differentially impact the capacity of different phytoplankton species to utilize DOP in the projected acidified and nutrient-limited future ocean.

ecology↗

bioRxiv2022

Structural Model for Self-Limiting β-strand Arrangement Within an Alzheimer's Amyloid-β Oligomer

Previous reports revealed that sodium dodecyl sulfate near its critical micelle concentration can drive the assembly of A{beta}42 along an oligomeric pathway. This pathway produces a 150 kDa peptide oligomer (approximately 32 peptide molecules or protomers) that does not aggregate further into amyloid fibrils. Solid-state nuclear magnetic resonance (NMR) spectroscopy revealed structural features distinguishing the 150 kDa oligomer from fibrils. A puzzling feature was the coexistence of parallel and antiparallel {beta}-sheets within the oligomer structure. Here we present new atomic-level structural constraints obtained via solid-state NMR spectroscopy, benefitting from improved resolution via sample concentration by ultracentrifugation. In addition, two-dimensional cryo-electron microscopy (cryo-EM) reconstruction revealed a 4-fold symmetric shape. We propose a structural model to rationalize the solid-sate NMR- and cryo-EM-derived structural constraints. This model has a hollow square cylinder shape, with antiparallel {beta}-sheets formed by residues 33-39 lining the inner walls and parallel {beta}-sheets formed by residues 11-22 lining the outer walls. Within successive layers, the outer {beta}-strands on each side of the square cylinder alternate between two forms: one within a U-shaped protomer and another within L-shaped protomer. Molecular dynamics simulations show that, when the oligomer model is embedded in a lipid membrane, ions permeate through the central pore, with cation selectivity. The model further motivates an assembly pathway-based interpretation that may explain why the 150 kDa oligomer does not undergo further aggregation into amyloid fibrils. Significance StatementA{beta} oligomers are thought to be the most toxic species in Alzheimers disease. Their sizes range from 2 to [~]50 protomers. Most published experimental data on A{beta} oligomers indicate that they, like fibrils, are composed of {beta}-sheets, but it is a mystery why any {beta}-sheet aggregate would exist as a stable oligomer without undergoing further aggregation into fibrils. Here, structural constraints from solid-state NMR and cryo-EM led us to an oligomer model with a hollow square cylinder shape capable of conducting ions when embedded in a lipid membrane. Based on the model, we argue that geometric frustration may distinguish the assembly pathway that produces this oligomer from fibril-forming assembly pathways.

biochemistry↗

bioRxiv2022

Tau polarizes an aging transcriptional signature to excitatory neurons and glia

Aging is a major risk factor for Alzheimers disease (AD), and cell-type vulnerability underlies its characteristic clinical manifestations. We have performed longitudinal, single-cell RNA-sequencing in Drosophila with pan-neuronal expression of human tau, which forms AD neurofibrillary tangle pathology. Whereas tau- and aging-induced gene expression strongly overlap (93%), they differ in the affected cell types. In contrast to the broad impact of aging, tau-triggered changes are strongly polarized to excitatory neurons and glia. Further, tau can either activate or suppress innate immune gene expression signatures in a cell type-specific manner. Integration of cellular abundance and gene expression pinpoints Nuclear Factor Kappa B signaling as a potential marker for neuronal vulnerability. We also highlight the conservation of cell type-specific transcriptional patterns between Drosophila and human postmortem brain tissue. Overall, our results create a resource for dissection of dynamic, age-dependent gene expression changes at cellular resolution in a genetically tractable model of tauopathy.

genomics↗

bioRxiv2022

SurvivalML: an integrative platform for the discovery and exploration of prognostic models in multi-center cancer cohorts

Advances in multi-omics and big-data technologies have led to numerous prognostic signatures aimed at improving current clinicopathological staging systems. Due to the lack of reproducibility and independent confirmation, few signatures have been translated into clinical routine. As high-quality datasets accumulate, identifying robust signatures across multiple independent cohorts becomes possible. Nonetheless, inaccurate data retrieval, different versions of genome annotations, disparate expression distributions, difficult data cleaning, inconsistent clinical information, algorithm selection, and parameter tuning have impeded model development and validation in multi-center datasets. Hence, for the first time, we introduced SurvivalML (https://rookieutopia.com/app_direct/SurvivalML/), a web application for helping develop and validate prognostic models across multi-center datasets. SurvivalML included 37,325 samples (253 eligible datasets) with both transcriptome data and survival information from 21 cancer types, which were renewedly and uniformly re-annotated, normalized, and cleaned. This application provided 10 survival machine-learning algorithms for flexibly training models via tuning essential parameters online and delivered four aspects for model evaluation, including Kaplan-Meier survival analysis, time-dependent ROC, calibration curve, and decision curve analysis. Overall, we believe that SurvivalML can serve as an attractive platform for model discovery from multi-center datasets.

bioinformatics↗

bioRxiv2022

BEST: a web application for comprehensive biomarker exploration on large-scale data in solid tumors

SummaryData mining from RNA-seq or microarray data has become an essential part of cancer biomarker exploration. Certain existing web servers are valuable and broadly utilized, but the meta-analysis of multiple datasets is absent. Most web servers only contain tumor samples from the TCGA database with only one cohort for each cancer type, which also means that the analysis results mainly derived from a single cohort are thin and unstable. Indeed, consistent performance across multiple independent cohorts is the foundation for an excellent biomarker. Moreover, many analytical functions researchers require remain adequately unmet by these tools. Thus, we introduce BEST (Biomarker Exploration for Solid Tumors), a web application for comprehensive biomarker exploration on large-scale data in solid tumors. BEST includes more than 50,000 samples of 27 cancer types. To ensure the comparability of genes between different sequencing technologies and the legibility of clinical traits, we re-annotated transcriptome data based on the GRCh38 patch 13 sequences and unified the nomenclature of clinical traits. BEST delivers fast and customizable functions, including clinical association, survival analysis, enrichment analysis, cell infiltration, immunomodulator, immunotherapy, candidate agents, and genomic alteration. Together, our web server provides multiple cleaned-up independent datasets and diverse analysis functionalities, helping unleash the value of current data resources. It is freely available at https://rookieutopia.com/. The bigger pictureBioinformatics web servers enable researchers without computational programming skills to conduct various bioinformatics analyses. However, most web servers only contain tumor samples from the TCGA database with only one cohort for each cancer type, which also means that the analysis results mainly derived from a single cohort are thin and unstable. Thus, we introduce BEST (Biomarker Exploration for Solid Tumors), a web application for comprehensive biomarker exploration on large-scale data in solid tumors. BEST includes more than 50,000 samples of 27 cancer types that have been uniformly re-annotated based on the GRCh38 patch 13 sequences, which ensures the comparability of genes between different sequencing technologies. BEST also offers prevalent functions including clinical association, survival analysis, enrichment analysis, cell infiltration, immunomodulator, immunotherapy, candidate agents, and genomic alteration. Together, BEST provides a curated database and innovative analytical pipelines to explore cancer biomarkers at high resolution.

genomics↗

bioRxiv2022

De novo protein identification in mammalian sperm using high-resolution in situ cryo-electron tomography

Understanding molecular mechanisms of cellular pathways requires knowledge of the identities of participating proteins, their cellular localization and their 3D structures. Contemporary workflows typically require multiple techniques to identify target proteins, track their localization using fluorescence microscopy, followed by in vitro structure determination. To identify mammal-specific sperm proteins and understand their functions, we developed a visual proteomics workflow to directly address these challenges. Our in situ cryo-electron tomography and subtomogram averaging provided 6.0 [A] resolution reconstructions of axonemal microtubules and their associated proteins. The well-resolved secondary and tertiary structures allowed us to computationally match, in an unbiased manner, novel densities in our 3D reconstruction maps with 21,615 AlphaFold2-predicted protein models of the mouse proteome. We identified Tektin 5, CCDC105 and SPACA9 as novel microtubule inner proteins that form an extensive network crosslinking the lumen of microtubule and existing proteins. Additional biochemical and mass spectrometry analyses helped validate potential candidates. The novel axonemal sperm structures identified by this approach form an extensive interaction network within the lumen of microtubules, suggesting they have a role in the mechanical and elastic properties of the microtubule filaments required for the vigorous beating motions of flagella.

biophysics↗

bioRxiv2022

The Developmental Profile of Visual Cortex Astrocytes

Though once thought of as passive support cells for neurons, it is now clear that astrocytes signal via calcium (Ca2+) to trigger gliotransmission that impacts surrounding neurons and synapses. We therefore investigated how astrocytes in layer-5 (L5) mouse visual cortex mature electrophysiologically and morphologically over postnatal days (P) 3 - 30 and how these relate to changes in spontaneous Ca2+ events. Across this age range, resting membrane potential increased, and input resistance decreased. Astrocytes also revealed different membrane responses to voltage steps: notably, membrane responses became more passive with age. Two-photon (2p) imaging of dye-loaded patched cells and confocal imaging revealed that gap-junction coupling increased starting around P7. Morphological reconstructions revealed increased branch density but also shorter branches after P20, suggesting that astrocyte branches may get pruned as dense tiling is established. Finally, we visualized spontaneous Ca2+ transients with 2p microscopy and found that Ca2+ events decorrelated, became more frequent as well as briefer with age. As astrocytes mature, spontaneous Ca2+ activity thus changes from relatively cell-wide, synchronous waves to local transients. Several astrocyte properties were stably mature from ~P15 onwards, although morphology continued to develop further. Our findings provide a descriptive foundation of astrocyte maturation, useful for the study of astrocytic impact on visual cortex critical period plasticity.

neuroscience↗

bioRxiv2022

FishSCT: a zebrafish-centric database for exploration and visualization of fish single-cell transcriptome

With the advancement of single-cell sequencing technology in recent years, an increasing number of researchers have turned their attention to the study of cell heterogeneity. In this study, we created a fish single-cell transcriptome database centered on zebrafish (Danio rerio). FishSCT currently contains single-cell transcriptomic data on zebrafish and 8 other fish species. We used a unified pipeline to analyze 129 datasets from 44 projects from SRA and GEO, resulting in 964/26,965 marker/potential marker information for 245 cell types, as well as expression profiles at single-cell resolution. There are 117 zebrafish datasets in total, covering 25 different types of tissues/organs at 36 different time points during the growth and development stages. This is currently the largest and most comprehensive online resource for zebrafish single-cell transcriptome data, as well as the only database dedicated to the collection of marker gene information of specific cell type and expression profiles at single-cell resolution for a variety of fish. A user-friendly web interface for information browsing, cell type identification, and expression profile visualization has been developed to meet the basic demand in related studies on fish transcriptome at the single-cell resolution.

bioinformatics↗

bioRxiv2022

Gene interaction perturbation network deciphers a high-resolution taxonomy in colorectal cancer

Molecular subtypes of colorectal cancer (CRC) are currently identified via the snapshot transcriptional profiles, largely ignoring the dynamic changes of gene expressions. Conversely, biological networks remain relatively stable irrespective of time and condition. Here, we introduce an individual-specific gene interaction perturbation network-based (GIN) approach and identify six GIN subtypes (GINS1-6) with distinguishing features: (i) GINS1 (proliferative, 24%[~]34%), elevated proliferative activity, high tumor purity, immune-desert, PIK3CA mutations, and immunotherapeutic resistance; (ii) GINS2 (stromal-rich, 14%[~]22%), abundant fibroblasts, immune-suppressed, stem-cell-like, SMAD4 mutations, unfavorable prognosis, high potential of recurrence and metastasis, immunotherapeutic resistance, and sensitive to fluorouracil-based chemotherapy; (iii) GINS3 (KRAS-inactivated, 13%[~]20%), high tumor purity, immune-desert, activation of EGFR and ephrin receptors, chromosomal instability (CIN), fewer KRAS mutations, SMOC1 methylation, immunotherapeutic resistance, and sensitive to cetuximab and bevacizumab; (iv) GINS4 (mixed, 10%[~]19%), moderate level of stromal and immune activities, transit-amplifying-like, and TMEM106A methylation; (v) GINS5 (immune-activated, 12%[~]24%), stronger immune activation, plentiful tumor mutation and neoantigen burden, microsatellite instability and high CpG island methylator phenotype, BRAF mutations, favorable prognosis, and sensitive to immunotherapy and PARP inhibitors; (vi) GINS6, (metabolic, 5%[~]8%), accumulated fatty acids, enterocyte-like, and BMP activity. Overall, the novel high-resolution taxonomy derived from an interactome perspective could facilitate more effective management of CRC patients.

genetics↗

bioRxiv2022

The genome of a vestimentiferan tubeworm (Ridgeia piscesae) provides insights into its adaptation to a deep-sea environment

Vestimentifera (Polychaeta, Siboglinidae) is a taxon of deep-sea worm-like animals living in the deep-sea hydrothermal vent and cold seep areas. The morphology and lifespan of Ridgeia piscesae, which is the only vestimentiferan tubeworm species found in the hydrothermal vents on the Juan de Fuca Ridge, vary greatly according to the endemic environments. Recent analyses have revealed the genomic basis of adaptation in three vent- and seep-dwelling vestimentiferan tubeworms. However, the evolutionary history and mechanism of adaptation in R. piscesae, a unique species in the family Siboglinidae, is remained to be investigated. Here we report a high-quality genome of R. piscesae collected at Cathedral vent of the Juan de Fuca Ridge. Comparative genomic analysis revealed that that the high growth rates of vent-dwelling tubeworms might derive from small genome size. The small genome sizes of these tubeworms are attributed to the repeat content but not the number of genes and intron sizes. Additionally, four genes involved in cell proliferation were subject to positive selection in the genome of R. piscesae, suggesting that, besides apoptosis, cell proliferation is important for regulating growth rate in this species.

genomics↗

bioRxiv2022

Limitations of Busulfan to Create Humanize Mice with an Innate Immune System.

Humanized mouse models have improved biomedical research by providing a tractable system with which to perform in vivo experiments on human tissues. Use of irritators is the standard method for establishing high levels of stem cell engraftment, however not all institutes have access to this instrumentation in the animal facility. The use of busulfan has been successfully used to precondition for stem cell engraftment on a limited number of mouse backgrounds. In this report we further test the utility of busulfan as a means to successfully engraft hIL15-Tg-NSG and SGM3-NSG mouse stains which are capable of establishing the innate NK cell and myeloid immune compartments. Results from our studies show that busulfan can successfully precondition hIL15-Tg-NSG mice but not SGM3-NSG mice for high levels of human immune cell engraftment. SGM3-NSG mice preconditioned with busulfan exhibited only 10-20% human CD45 cells in the bone marrow or spleen, where as NSG and hIL15-Tg-NSG mice routinely achieved [~]80%. Busulfan preconditioned SGM3-NSG mice showed elevated levels of granulocytic MDSC, and cDC1 and cDC2 myeloid populations. This is in contrast with hIL15-TG-NSG which showed robust reconstitution of mature CD16 expressing NK cells. We conclude from our studies that busulfan is an effective means to precondition mice for CD34+ stem cell engraftment, but it may have limitations when use to precondition the SGM3-NSG model.

immunology↗

bioRxiv2022

Viscoelastic Notch Signaling Hydrogel Induces Liver Bile Duct Organoid Growth and Morphogenesis

Cholangiocyte organoids can be used to model liver biliary disease; however, both a defined matrix in which to emulate cholangiocyte self-assembly and the mechano-transduction pathways involved therein remain elusive. We designed a series of defined viscoelastic hyaluronan hydrogels in which to culture primary cholangiocytes and found that by mimicking the stress relaxation rate of liver tissue, we could induce cholangiocyte organoid growth and significantly increase expression of Yes-associated protein (YAP) target genes. Strikingly, inhibition of matrix metalloproteinases (MMPs) did not significantly affect organoid growth in 3D culture, suggesting that mechanical remodeling of the viscoelastic microenvironment - and not MMP-mediated degradation - is key to cholangiocyte organoid growth. By immobilizing jagged1 to the hyaluronan, stress relaxing hydrogel, self-assembled bile duct structures formed in organoid culture, indicating the synergistic effects of Notch signaling and viscoelasticity. By uncovering critical roles of hydrogel viscoelasticity, YAP signaling and Notch activation, we controlled cholangiocyte organogenesis, thereby paving the way for their use in disease modeling and/or transplantation.

bioengineering↗

bioRxiv2022

Plasmacytoid dendritic cells regulate megakaryocyte and platelet homeostasis

Platelet homeostasis is essential for vascular integrity and immune defense. While the process of platelet formation by fragmenting megakaryocytes (thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of megakaryocytes by their progenitor cells (megakaryopoiesis) remains unclear. Here we use intravital 2 photon microscopy to track individual megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as crucial bone marrow niche cells that regulate megakaryopoiesis. pDCs monitor the bone marrow for platelet-producing megakaryocytes and deliver IFN- to the megakaryocytic niche to trigger local on-demand proliferation of megakaryocyte progenitors. This fine-tuned coordination between thrombopoiesis and megakaryopoiesis is crucial for megakaryocyte and platelet homeostasis in steady state and stress. However, uncontrolled pDC function within the megakaryocytic niche is detrimental. Accordingly, we show that pDCs activated by SARS-CoV2 drive inappropriate megakaryopoiesis associated with thrombotic complications. Together, we uncover a hitherto unknown megakaryocytic bone marrow niche maintained by the constitutive delivery of pDC-derived IFN-.

immunology↗

bioRxiv2022

Disruption of place cell remapping by scopolamine during aversive learning

Aversive stimuli can cause hippocampal place cells to remap their firing fields, but it is not known whether remapping plays a role in storing memories of aversive experiences. Here we addressed this question by performing in-vivo calcium imaging of CA1 place cells in freely behaving rats (n=14). Rats were first trained to prefer a short path over a long path for obtaining food reward, then trained to avoid the short path by delivering a mild footshock. Remapping was assessed by comparing place cell population vector similarity before acquisition versus after extinction of avoidance. Some rats received shock after systemic injections of the amnestic drug scopolamine at a dose (1 mg/kg) that impaired avoidance learning but spared spatial tuning and shock-evoked responses of CA1 neurons. Place cells remapped significantly more following remembered than forgotten shocks (drug-free versus scopolamine conditions); shock-induced remapping did not cause place fields to migrate toward or away from the shocked location and was similarly prevalent in cells that were responsive versus non-responsive to shocks. When rats were exposed to a neutral barrier rather than aversive shock, place cells remapped significantly less in response to the barrier. We conclude that place cell remapping occurs in response to events that are remembered rather than merely perceived and forgotten, suggesting that reorganization of hippocampal population codes may play a role in storing memories for aversive events.

neuroscience↗

bioRxiv2022

Role of Paravertebral muscle myostatin upregulation in the development of idiopathic scoliosis

Paravertebral muscle (PVM) abnormalities play important roles in the pathogenesis of idiopathic scoliosis (IS), and elevated oxidative stress could result in PVM injury in IS patients, but the underlying mechanism of oxidative stress generation is still unclear. Increased apoptosis, impaired myogenesis and elevated oxidative stress were found in primary skeletal muscle mesenchymal progenitor cells (hSM-MPCs), which are essential for the myogenesis process of vertebrate skeletal muscles, of IS patients. Through RNA-sequencing and further analysis, we identified significantly upregulated myostatin (MSTN) in IS hSM-MPCs. Overexpression of MSTN in hSM-MPCs from control patients increased the expression of NADPH oxidase 4, promoted reactive oxygen species production and apoptosis, and suppressed myogenesis. However, MSTN knockdown decreased the expression of NADPH oxidase 4, inhibited reactive oxygen species production and apoptosis, and enhanced myogenesis in IS hSM-MPCs. In addition, overexpression of MSTN in the PVMs of mice induced elevated oxidative stress and scoliosis without abnormal vertebral structure. Altogether, our study suggested that abnormal PVM changes and accumulated oxidative stress in IS patients may result from upregulation of MSTN, which could contribute to the development of IS.

pathology↗

bioRxiv2022

In situ cryo-electron tomography reveals the asymmetric architecture of mammalian sperm axonemes

The flagella of mammalian sperm display non-planar, asymmetric beating, in contrast to the planar, symmetric beating of flagella from sea urchin sperm and unicellular organisms. The molecular basis of this difference is unclear. Here, we perform in situ cryo-electron tomography of mouse and human sperm axonemes, providing the highest resolution structural information to date. Our subtomogram averages reveal mammalian sperm- specific protein complexes within the outer microtubule doublets, the radial spokes and nexin-dynein regulatory complexes. The locations and structures of these complexes suggest potential roles in enhancing the mechanical strength of mammalian sperm axonemes and regulating dynein-based axonemal bending. Intriguingly, we find that each of the nine outer microtubule doublets is decorated with a distinct combination of sperm- specific complexes. We propose that this asymmetric distribution of proteins differentially regulates the sliding of each microtubule doublet and may underlie the asymmetric beating of mammalian sperm.

biophysics↗

bioRxiv2022

Testing the link between isoaspartate and Alzheimer's disease etiology

Isoaspartate (isoAsp) is a damaging amino acid residue formed in proteins as a result of spontaneous deamidation. IsoAsp disrupts the secondary and higher order structures of proteins, damaging their functions and making them prone to aggregation. An association has been suggested between isoAsp and Alzheimers Disease (AD). Here we strengthened the link between isoAsp and AD by novel approaches to isoAsp analysis in blood human serum albumin (HSA), the most abundant blood protein, a major carrier of amyloid beta (A{beta}) peptide and phosphorylated tau (pTau) protein in blood and a key participant in their clearance pathway. We discovered a reduced amount of anti-isoAsp antibodies (P < .0001), an elevated isoAsp level in HSA (P < .001), more HSA aggregates (P < .0001) and increased levels of free A{beta} (P < .01) in AD blood compared to healthy controls. We also found that deamidation significantly reduces HSA capacity to bind with A{beta} and pTau (P < .05). These findings support the presence in AD of a bottleneck in clearance of A{beta} and pTau leading to their increased concentrations in brain and facilitating their aggregations there. RESEARCH IN CONTEXTO_LISystematic review: We reviewed the evidence that associates isoaspartate (isoAsp) residue in blood proteins with the etiology of Alzheimers disease (AD). However, the link between isoAsp in blood and aggregation of amyloid beta (A{beta}) peptide and phosphorylated tau (pTau) protein in brain remained unclear. C_LIO_LIInterpretation: For the first time we demonstrate that isoAsp-containing human serum albumin (HSA) forms aggregates with reduced binding capacity toward A{beta} peptide and pTau protein. Using a novel ELISA, we discovered in AD blood elevated levels of isoAsp in HSA, together with reduced endogenous anti-isoAsp antibody levels, suggesting hampered A{beta} and pTau clearance in AD. C_LIO_LIFuture directions: As degradation of the innate anti-isoAsp defenses may take years to develop, investigation of the isoAsp role in early stages of AD is warranted. And enrollment of different neurodegenerative disease cohorts will illustrate if isoAsp is AD-specific or universal to diseases related to aging. C_LI O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

neuroscience↗

bioRxiv2022

Bioprinting microporous functional living materials from protein-based core-shell microgels

Living materials bring together material science and biology to allow the engineering and augmenting of living systems with novel functionalities. Bioprinting promises accurate control over the formation of such complex materials through programmable deposition of cells in soft materials, but current approaches had limited success in fine-tuning cell microenvironments while generating robust macroscopic morphologies. Here, we address this challenge through the use of core-shell microgel ink to decouple cell microenvironments from the structural shell for further processing. Cells are microfluidically immobilized in the viscous core that can promote the formation of both microbial populations and mammalian cellular spheroids, followed by interparticle annealing to give covalently stabilized functional scaffolds with controlled microporosity. The results show that the core-shell strategy mitigates cell leakage while affording a favorable environment for cell culture. Furthermore, we demonstrate that different microbial consortia can be printed into scaffolds for a range of applications. By compartmentalizing microbial consortia in separate microgels, the collective bioprocessing capability of the scaffold is significantly enhanced, shedding light on strategies to augment living materials with bioprocessing capabilities.

bioengineering↗