Biology subjects

Kim, H.

Publications and source records attributed to Kim, H..

At least 523 records · Page 29Linked to original sources

bioRxiv2019

Mammary epithelial cells have lineage-restricted metabolic identities

Cancer metabolism adapts the metabolic network of its tissue-of-origin. However, breast cancer is not a disease of a singular origin. Multiple epithelial populations serve as the culprit cell-of-origin for specific breast cancer subtypes, yet knowledge surrounding the metabolic network of normal mammary epithelial cells is limited. Here, we show that mammary populations have cell type-specific metabolic programs. Primary human breast cell proteomes of basal, luminal progenitor, and mature luminal populations revealed their unique enrichment of metabolic proteins. Luminal progenitors had higher abundance of electron transport chain subunits and capacity for oxidative phosphorylation, whereas basal cells were more glycolytic. Targeting oxidative phosphorylation and glycolysis with inhibitors exposed distinct metabolic vulnerabilities of the mammary lineages. Computational analysis indicated that breast cancer subtypes retain metabolic features of their putative cell-of-origin. Lineage-restricted metabolic identities of normal mammary cells partly explain breast cancer metabolic heterogeneity and rationalize targeting subtype-specific metabolic vulnerabilities to advance breast cancer therapy.

cell biology↗

bioRxiv2019

Alcohol induces mitochondrial fragmentation and stress responses to maintain normal muscle function in Caenorhabditis elegans

AbstractsChronic excessive ethanol consumption produces distinct toxic and adverse effects on different tissues. In skeletal muscle ethanol causes alcoholic myopathy characterized by myofiber atrophy and loss of muscle strength. Alcoholic myopathy is more prevalent than all inherited muscle diseases combined. Current evidence indicates that ethanol directly impairs muscle organization and function. However, the underlying mechanism by which ethanol causes its toxicity to muscle is poorly understood. Here, we show that the nematode C. elegans recapitulates key aspects of alcoholic myopathy when exposed to ethanol. As in mammals, ethanol exposure impairs muscle strength and organization and induces the expression of protective genes, including oxidative stress response. In addition, ethanol exposure causes a fragmentation of mitochondrial networks aligned with myofibril lattices. This ethanol-induced mitochondrial fragmentation is dependent on mitochondrial fission factor DRP-1 (dynamin-like protein 1), and its receptor proteins on the mitochondrial outer membrane. Our data indicate that this fragmentation contributes to activation of mitochondrial unfolded protein response (UPR). We also found that robust perpetual mitochondrial UPR activation effectively counters muscle weakness caused by ethanol exposure. Our results strongly suggest that modulation of mitochondrial stress responses provides a mechanism to ameliorate alcohol toxicity and damage to muscle.\n\nSignificanceChronic alcohol abuse causes the damage and toxicity to peripheral tissues, including muscle. Alcohol perturbs the structure and function of striated skeletal and cardiac muscles. These toxic effects of alcohol on striated muscles negatively impact morbidity and mortality to alcohol misusers. Here, we demonstrate that the nematode C. elegans also exhibits key features of alcoholic myopathy when exposed to ethanol. Ethanol exposure impairs muscle organization and strength, and induces the expression of genes that cope with alcohol toxicity. Particularly, we find that ethanol toxicity is centered on mitochondria, the power plants of the cell. As an adaptive protective response to mitochondrial dysfunction, ethanol-exposed cells induce global transcriptional reprogramming to restore normal mitochondrial function. Upregulation of this transcriptional reprogramming in C. elegans effectively blocks ethanol-induced muscle weakness, a key feature of alcoholic myopathy. Thus, the modulation of mitochondrial stress responses is a potentially promising therapeutic strategy to ameliorate alcohol toxicity to muscle.

genetics↗

bioRxiv2019

Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging

IntroductionChimeric antigen receptor (CAR) T-cells have been developed recently, producing impressive outcomes in patients with hematologic malignancies. However, there is no standardized method for cell trafficking and in vivo CAR T-cell monitoring. We assessed the feasibility of real-time in vivo 89Zr-p-Isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS, DFO) labeled CAR T-cell trafficking using positron emission tomography (PET).\n\nResultsThe 89Zr-DFO radiolabeling efficiency of Jurkat/CAR and human peripheral blood mononuclear cells (hPBMC)/CAR T-cells was 70-79%, and cell radiolabeling activity was 98.1-103.6 kBq/106 cells. Cell viability after radiolabeling was >95%. Compared with unlabeled cells, cell proliferation was not significantly different during the early period after injection; however, the proliferative capacity decreased over time (p = 0.02, day 7 after labeling). IL-2 or IFN-{gamma} secretion was not significantly different between unlabeled and labeled CAR T-cells. PET/magnetic resonance images in the xenograft model showed that most of the 89Zr-DFO-labeled Jurkat/CAR T-cells were distributed in the lung (24.4% {+/-} 3.4%ID) and liver (22.9% {+/-} 5.6%ID) by 1 hour after injection. The cells gradually migrated from lung to the liver and spleen by day 1, and remained stably until day 7 (on day 7: lung 3.9% {+/-} 0.3%ID, liver 36.4% {+/-} 2.7%ID, spleen 1.4% {+/-} 0.3%ID). No significant accumulation of labeled cells was identified in tumors. A similar pattern was observed in ex vivo biodistributions on day 7 (lung 3.0% {+/-} 1.0%ID, liver 19.8% {+/-} 2.2%ID, spleen 2.3% {+/-} 1.7%ID). 89Zr-DFO-labeled hPBMC/CAR T-cells showed the similar distribution on serial PET images as Jurkat/CAR T-cells. The distribution of CAR T-cells was cross-confirmed by flow cytometry, Alu polymerase chain reaction, and immunohistochemistry.\n\nConclusionUsing PET imaging of 89Zr-DFO-labeled CAR T-cells, real time in vivo cell trafficking is feasible. It can be used to investigate cellular kinetics, initial in vivo biodistribution, and the safety profile in future CAR T-cell development.

cancer biology↗

bioRxiv2019

Commensal-derived succinate enhances tuft cell specification and suppresses ileal inflammation

Longitudinal analysis of Crohn's disease (CD) incidence has identified an inverse correlation with helminth infestation and recent studies have revealed that intestinal tuft cell hyperplasia is critical for helminth response. Tuft cell frequency was decreased in the inflamed ilea of CD patients and a mouse model of TNF-induced Crohn's-like ileitis (TNF{Delta}ARE). Single-cell RNA sequencing paired with unbiased differential trajectory analysis of the tuft cell lineage in a genetic model of tuft cell hyperplasia (AtohKO) demonstrated that the tuft cell lineage had increased tricarboxylic acid (TCA) cycle gene signatures. Commensal microbiome-derived succinate was detected in the ileal lumen of these animals while microbiome depletion suppressed tuft cell hyperplasia. Therapeutic succinate treatment in TNF{Delta}ARE animals reduced pathology in correlation with induced tuft cell specification. We provide evidence implicating the modulatory role of intestinal tuft cells in chronic intestinal inflammation, which could facilitate leveraging this rare and elusive cell type for CD treatment.

cell biology↗

bioRxiv2019

Improving personalized prediction of cancer prognoses with clonal evolution models

Cancer occurs via an accumulation of somatic genomic alterations in a process of clonal evolution. There has been intensive study of potential causal mutations driving cancer development and progression. However, much recent evidence suggests that tumor evolution is normally driven by a variety of mechanisms of somatic hypermutability, known as mutator phenotypes, which act in different combinations or degrees in different cancers. Here we explore the question of how and to which degree different mutator phenotypes act in a cancer predict its future progression. We develop a computational paradigm using evolutionary tree inference (tumor phylogeny) algorithms to derive features quantifying single-tumor mutational preferences, followed by a machine learning frame-work to identify key features predictive of progression. We build phylogenies tracing the evolution of subclones of cells in tumor tissues using a variety of somatic genomic alterations, including single nucleotide variations, copy number alterations, and structural variations. We demonstrate that mutation preference features derived from the phylogenies are predictive of clinical outcomes of cancer progression - overall survival and disease-free survival - based on the analyses on breast invasive carcinoma, lung adenocarcinoma, and lung squamous cell carcinoma. We further show that mutational phenotypes have predictive power even after accounting for traditional clinical and driver-centric predictors of progression. These results confirm the power of mutational phenotypes as an independent class of predictive biomarkers and suggest a strategy for enhancing the predictive power of conventional clinical or driver-centric genomic features.

cancer biology↗

bioRxiv2019

RNA-dependent RNA polymerase speed and fidelity are not the only determinants of the mechanism or efficiency of recombination.

Using the RNA-dependent RNA polymerase (RdRp) from poliovirus (PV) as our model system, we have shown that Lys-359 in motif-D functions as a general acid in the mechanism of nucleotidyl transfer. A K359H (KH) RdRp derivative is slow and faithful relative to wild-type enzyme. In the context of the virus, RdRp-coding sequence evolves, selecting for the following substitutions: I331F (IF, motif-C) and P356S (PS, motif-D). We have evaluated IF-KH, PS-KH, and IF-PS-KH viruses and enzymes. The speed and fidelity of each double mutant are equivalent. Each exhibits a unique recombination phenotype, with IF-KH being competent for copy-choice recombination and PS-KH being competent for forced-copy-choice recombination. Although the IF-PS-KH RdRp exhibits biochemical properties within twofold of wild type, the virus is impaired substantially for recombination in cells. We conclude that there are biochemical properties of the RdRp in addition to speed and fidelity that determine the mechanism and efficiency of recombination. The interwoven nature of speed, fidelity, the undefined property suggested here, and recombination makes it impossible to attribute a single property of the RdRp to fitness. However, the derivatives described here may permit elucidation of the importance of recombination on the fitness of the viral population in a background of constant polymerase speed and fidelity.\n\nSignificanceThe availability of a \"universal\" method to create attenuated viruses for use as vaccine strains would permit a rapid response to outbreaks of newly emerging viruses. Targeting RdRp fidelity has emerged as such a universal approach. However, because polymerase fidelity and speed are inextricably linked, the effort to attribute the attenuated phenotype to a single biochemical property of the RdRp may be futile. Here, we show that this circumstance is even more complex. We provide evidence for the existence of a biochemical parameter that combines with fidelity and speed to govern the mechanism and/or efficiency of recombination. We conclude that the field will be served best by continued emphasis on discovery of manipulatable functions of the RdRp instead of debating the importance of individual properties.

microbiology↗

bioRxiv2019

Plasma membrane damage causes NLRP3 activation and pyroptosis during Mycobacterium tuberculosis infection

Mycobacterium tuberculosis (Mtb) is a major global health problem and causes extensive cytotoxicity in patient cells and tissues. Here we define an NLRP3, caspase-1 and gasdermin D-mediated pathway to pyroptosis in human monocytes following exposure to Mtb. We demonstrate an ESX-1 mediated, contact-induced plasma membrane (PM) damage response that occurs during phagocytosis or from the cytosolic side of the PM after phagosomal rupture in Mtb infected cells. This PM injury in turn causes K+ efflux and activation of NLRP3 dependent IL-1{beta} release and pyroptosis, facilitating the spread of Mtb to neighbouring cells. Further we reveal a dynamic interplay of pyroptosis with ESCRT-mediated PM repair. Collectively, these findings reveal a novel mechanism for pyroptosis and spread of infection acting through dual PM disturbances both during and after phagocytosis. We also highlight dual PM damage as a common mechanism utilized by other NLRP3 activators that have previously been shown to act through lysosomal damage.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC=\"FIGDIR/small/747014v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (28K):\norg.highwire.dtl.DTLVardef@1911356org.highwire.dtl.DTLVardef@18c99dcorg.highwire.dtl.DTLVardef@1c94bb9org.highwire.dtl.DTLVardef@8a69db_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2019

Cryo-EM structure of the human Mixed Lineage Leukemia-1 complex bound to the nucleosome

Mixed Lineage Leukemia (MLL) family histone methyltransferases are the key enzymes that deposit histone H3 Lys4 (K4) mono-/di-/tri-methylation and regulate gene expression in mammals. Despite extensive structural and biochemical studies, the molecular mechanism by which the MLL complexes recognize histone H3K4 within the nucleosome core particle (NCP) remains unclear. Here, we report the single-particle cryo-electron microscopy (cryo-EM) structure of the human MLL1 core complex bound to the NCP. The MLL1 core complex anchors on the NCP through RbBP5 and ASH2L, which interacts extensively with nucleosomal DNA as well as the surface close to histone H4 N-terminal tail. Concurrent interactions of RbBP5 and ASH2L with the NCP uniquely align the catalytic MLL1SET domain at the nucleosome dyad, allowing symmetrical access to both H3K4 substrates within the NCP. Our study sheds light on how the MLL1 complex engages chromatin and how chromatin binding promotes MLL1 tri-methylation activity.

biochemistry↗

bioRxiv2019

The finger 2 tip loop of Activin A is required for the formation of its non-signaling complex with ACVR1 and type II Bone Morphogenetic Protein receptors

Activin A functions in BMP signaling in two ways: it either engages ACVR1B to activate Smad2/3 signaling or binds ACVR1 to form a non-signaling complex (NSC). Although the former property has been studied extensively, the roles of the NSC remain unexplored. The genetic disorder fibrodysplasia ossificans progressiva (FOP) provides a unique window into ACVR1/Activin A signaling because in that disease Activin can either signal through FOP-mutant ACVR1 or form NSCs with wild type ACVR1. To explore the role of the NSC, we generated agonist-only Activin A muteins that activate ACVR1B but cannot form the NSC with ACVR1. Using one of these muteins we demonstrate that failure to form the NSC in FOP results in more severe disease pathology. These results provide the first evidence for a biological role for the NSC in vivo and pave the way for further exploration of the NSCs physiological role in corresponding knock-in mice. Impact StatementThe non-signaling complex formed by Activin A and ACVR1 is operant in vivo and is required to temper the degree of heterotopic ossification in the genetic disorder fibrodysplasia ossificans progressiva.

cell biology↗

bioRxiv2019

The polyQ expansion modulates the configuration and phosphorylation of huntingtin

The polyQ-expansion at the N-terminus of huntingtin (HTT) is the prime cause of Huntingtons disease. The recent cryo-EM structure of HTT with HAP40 provides information on the proteins prominent HEAT-repeats. Here, we present analyses of the impact of polyQ-length on the conformation of HTT by cryo-EM, the domain-interactions by cross-linking mass spectrometry and the phosphorylation of HTT. The cryo-EM analysis of normal (Q23-) and disease (Q78-) type HTTs in their apo forms shows that the structures of apo HTTs significantly differ from the structure of HTT-HAP40, and that the polyQ expansion induces global structural changes consisting of significant domain movements of the C-HEAT domain relative to the N-HEAT domain. In addition, we show that the polyQ-expansion alters the phosphorylation pattern across the full-length HTT and that the specific phosphorylation (Ser2116p) in turn affects the global structure of HTT, which influences the activity of polyQ-expanded HTT. These results provide a molecular basis for the effect of the N-terminal polyQ segment on HTT structure and activity, that may be important for the cell-selective toxicity of mutant HTT.

neuroscience↗

bioRxiv2019

Criticality as a determinant of integrated information {Phi} in human brain networks

Integrated information theory (IIT) postulates that consciousness arises from the cause-effect structure of a system but the optimal network conditions for this structure have not been elucidated. In the study, we test the hypothesis that network criticality, a dynamically balanced state between a large variation of functional network configurations and a large constraint of structural network configurations, is a necessary condition for the emergence of a cause-effect structure that results in a large {Phi}, a surrogate of integrated information. We also hypothesized that if the brain deviates from criticality, the cause-effect structure is obscured and {Phi} diminishes. We tested these hypotheses with a large-scale brain network model and high-density electroencephalography (EEG) acquired during various levels of human consciousness during general anesthesia. In the modeling study, maximal criticality coincided with maximal {Phi}. The constraint of the structural network on the functional network is maximized in the maximal criticality. The EEG study demonstrated an explicit relationship between {Phi}, criticality, and level of consciousness. Functional brain network significantly correlated with structural brain network only in conscious states. The results support the hypothesis that network criticality maximizes {Phi}.

neuroscience↗

bioRxiv2019

TMEM16F phospholipid scramblase mediates trophoblast fusion and placental development

Cell-cell fusion or syncytialization is fundamental to the reproduction, development and homeostasis of multicellular organisms. In addition to various cell-type specific fusogenic proteins, cell surface externalization of phosphatidylserine (PS), a universal eat-me signal in apoptotic cells, has been observed in different cell-fusion events. Nevertheless, molecular underpinnings of PS externalization and cellular mechanisms of PS-facilitated cell-cell fusion are unclear. Here we report that TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), plays an indispensable role in placental trophoblast fusion by translocating PS to the cell surface independent of apoptosis. Consistent with its essential role in trophoblast fusion, the placentas from TMEM16F-deficient mice exhibit deficiency in syncytialization, placental developmental defects and perinatal lethality. Our findings thus identify a cell-cell fusion mechanism by which TMEM16F CaPLSase-dependent externalization of PS serves as a critical cell fusion signal to facilitate trophoblast syncytialization and placental development.

cell biology↗

bioRxiv2019

New genetic sources for orange color in cucumber (Cucumis sativus L.) fruit flesh

Most cucumber varieties have fruits with white flesh, which is devoid of {beta}-carotene and has a low concentration of total carotenoids. Carotenoids are important nutrients for humans and animals. Thus, developing cucumber varieties with orange flesh could provide a new nutritionally enhanced food source. Some cucumbers with yellow and orange flesh have been described, but there are others that have not been studied. Here, we used three cucumber PI lines, reported to produce colored fruits, from the USDA National Plant Germplasm System to generate three F2 populations. Fruits from the F2 populations with colored flesh (green, yellow, or orange) were pooled, and an equal number of fruits with white flesh were pooled. RNA was isolated from the pools and used for RNA sequencing to determine gene expression differences and to identify SNPs in each pool. The orange color of the cucumber fruits was confirmed to be due to {beta}-carotene. There were no clear expression patterns for genes of the carotenoid biosynthesis pathway that would suggest that their expression controlled the coloration of fruits. Mutations in carotenoid biosynthesis genes also did not explain the variation. However, we detected a SNP in the homolog of the Or gene that is responsible for {beta}-carotene accumulation in orange cauliflower. This genetic basis is different from that of previously studied orange cucumbers, but our results suggest that Or is not the only factor. These results provide the basis for future studies for breeding orange cucumbers for commercial or home garden production.

plant biology↗

bioRxiv2019

Genomic profiling of 553 uncharacterized neurodevelopment patients reveals a high proportion of recessive pathogenic variant carriers in an outbred population

BackgroundA substantial portion of Mendelian disease patients suffers from genetic variants that are inherited in a recessive manner. A precise understanding of pathogenic recessive variants in a population would assist in pre-screening births of such patients. However, a systematic understanding of the contribution of recessive variants to Mendelian diseases is still lacking.\n\nMethodsGenetic diagnosis and variant discovery of 553 undiagnosed Korean patients with complex neurodevelopmental problems (KND for Korean NeuroDevelopmental cohort) were performed using whole exome sequencing of patients and their parents. Pathogenic variants were selected and evaluated based on a comparison to patient symptoms and genetic properties of the variants were analyzed.\n\nResultsDisease-causing variants, including newly discovered variants, were identified in in 57.5% of the probands of the KND cohort. Of the 553 patients, 47.4% harbored variants that were previously reported as being pathogenic, and 35.1% of the previous reported pathogenic variants were inherited in a recessive manner. Genes that cause recessive disorders tend to be less constrained by loss-of-function variants and enriched in metabolic and mitochondrial pathways. This observation was applied to an estimation that approximately 1 in 17 healthy Korean individuals carry at least one of these pathogenic variants that develop severe neurodevelopmental problems in a recessive manner. Furthermore, the feasibility of these genes for carrier screening was evaluated.\n\nConclusionsWe suggest that the odds are high for healthy individuals carrying a potentially pathogenic variant, and its genetic properties. Our results will serve as a foundation for recessive variant screening to reduce occurrences of rare Mendelian disease patients. Additionally, our results highlight the utility and necessity of whole exome sequencing-based diagnostics for improving patient care in a country with a centralized medical system.

genetics↗

bioRxiv2019

Comparative molecular life history of spontaneous canine and human gliomas

Sporadic gliomas in companion dogs provide a window on the interaction between tumorigenic mechanisms and host environment. We compared the molecular profiles of canine gliomas with those of human pediatric and adult gliomas to characterize evolutionarily conserved mammalian mutational processes in gliomagenesis. Employing whole genome-, exome-, transcriptome-and methylation-sequencing of 81 canine gliomas, we found alterations shared between canine and human gliomas such as the receptor tyrosine kinases, p53 and cell cycle pathways, and IDH1 R132. Canine gliomas showed high similarity with human pediatric gliomas per robust aneuploidy, mutational rates, relative timing of mutations, and DNA methylation patterns. Our cross-species comparative genomic analysis provides unique insights into glioma etiology and the chronology of glioma-causing somatic alterations.\n\nSignificanceDiffuse gliomas are the most common malignant brain tumors, with high-grade tumors carrying a dismal prognosis. Preclinical models have proven themselves as poor predictors of clinical efficacy. Spontaneous glioma in dogs provides an attractive alternative model, because of their comparable tumor microenvironment and tumor life history. We determined the similarities and differences between human and canine gliomas through genomic profiling, and leveraged our datasets to identify conserved somatic drivers, mutational processes and temporal ordering of somatic glioma events across species. We show that canine gliomas resemble human gliomas at (epi-)genetic levels and are more reminiscent of pediatric than adult disease, thus rationalizing sporadic canine glioma as a preclinical model tailored to measuring treatment efficacies in patients with canine or human glioma.

cancer biology↗

bioRxiv2019

IQSEC3 Mediates Npas4-dependent GABAergic Synaptic Transmission and Depressive-like Behavior

Organization of mammalian inhibitory synapses is thought to be crucial for normal brain functions, but the underlying molecular mechanisms have been still incompletely understood. IQSEC3 (IQ motif and Sec7 domain 3) is a guanine nucleotide exchange factor for ADP-ribosylation factor (ARF-GEF) that directly interacts with gephyrin. Here, we show that GABAergic synapse-specific transcription factor, Npas4 (neuronal PAS domain protein 4) directly binds to the promoter of Iqsec3 and regulates its transcription. Strikingly, an enriched environment (EE) induced Npas4 upregulation and concurrently increased IQSEC3 protein levels specifically in mouse CA1 stratum oriens layer somatostatin (SST)-expressing GABAergic interneurons, which are compromised in Npas4-knockout (KO) mice. Moreover, expression of wild-type (WT) IQSEC3, but not a dominant-negative (DN) ARF-GEF-inactive mutant, rescued the decreased GABAergic synaptic transmission in Npas4-deficient SST interneurons. Concurrently, expression of IQSEC3 WT normalized the altered GABAergic synaptic transmission in dendrites, but not soma, of Npas4-deficient CA1 pyramidal neurons. Furthermore, expression of IQSEC3 WT, but not IQSEC3 DN, in SST-expressing interneurons in CA1 SST Npas4-KO mice rescued the altered anxiety-like behavior. Collectively, our results suggest that IQSEC3 is a key GABAergic synapse component that is directed by Npas4 activity- and ARF activity-dependent gene programs in SST-expressing interneurons to orchestrate the functional excitation-to-inhibition balance.

neuroscience↗

bioRxiv2019

SpCas9 activity prediction by DeepCas9, a deep learning-based model with unparalleled generalization performance

We evaluated SpCas9 activities at 12,832 target sequences using a high-throughput approach based on a human cell library containing sgRNA-encoding and target sequence pairs. Deep learning-based training on this large data set of SpCas9-induced indel frequencies led to the development of a SpCas9-activity predicting model named DeepSpCas9. When tested against independently generated data sets (our own and those published by other groups), DeepSpCas9 showed unprecedentedly high generalization performance. DeepSpCas9 is available at http://deepcrispr.info/DeepCas9.

genetics↗

bioRxiv2019

2D or 3D? How in vitro cell motility is conserved across dimensions, and predicts in vivo invasion

Cell motility is a critical aspect of wound healing, the immune response, and is deregulated in cancer. Current limitations in imaging tools make it difficult to study cell migration in vivo. To overcome this, and to identify drivers from the microenvironment that regulate cell migration, bioengineers have developed 2D and 3D tissue model systems in which to study cell motility in vitro, with the aim of mimicking the environments in which cells move in vivo. However, there has been no systematic study to explicitly relate and compare cell motility measurements between these geometries/systems. Here, we provide such analysis on our own data, as well as across data in existing literature to understand whether, and which, in vitro models are predictive of in vivo cell motility. To our surprise, many metrics of cell movement on 2D surfaces significantly and positively correlate with cell migration in 3D environments, and cell invasion in 3D is negatively correlated with glioblastoma invasion in vivo. Finally, to best compare across complex model systems, in vivo data, and data from different labs, we suggest that groups report an effect size, a statistical tool that is most translatable across experiments and labs, when conducting experiments that affect cellular motility.

bioengineering↗