Biology subjects

Wang, C.

Publications and source records attributed to Wang, C..

At least 649 records · Page 36Linked to original sources

bioRxiv2023

The Spread of Interferon-γ in Melanomas is Highly Spatially Confined, Driving Non-Genetic Variability in Tumor Cells

Interferon-{gamma} (IFN{gamma}) is a critical anti-tumor cytokine that has varied effects on different cell types. The global effect of IFN{gamma} in the tumor depends on which cells it acts upon and the spatial extent of its spread. Reported measurements of IFN{gamma} spread vary dramatically in different contexts, ranging from nearest-neighbor signaling to perfusion throughout the entire tumor. Here, we apply theoretical considerations to experiments both in vitro and in vivo to study the spread of IFN{gamma} in melanomas. We observe spatially confined niches of IFN{gamma} signaling in 3-D mouse melanoma cultures and human tumors that generate cellular heterogeneity in gene expression and alter the susceptibility of affected cells to T cell killing. Widespread IFN{gamma} signaling only occurs when niches overlap due to high local densities of IFN{gamma}-producing T cells. We measured length scales of [~]30-40m for IFN{gamma} spread in B16 mouse melanoma cultures and human primary cutaneous melanoma. Our results are consistent with IFN{gamma} spread being governed by a simple diffusion-consumption model, and offer insight into how the spatial organization of T cells contributes to intra-tumor heterogeneity in inflammatory signaling, gene expression, and immune-mediated clearance. Solid tumors are often viewed as collections of diverse cellular "neighborhoods": our work provides a general explanation for such non-genetic cellular variability due to confinement in the spread of immune mediators.

systems biology↗

bioRxiv2023

A multidimensional atlas of human glioblastoma organoids reveals highly coordinated molecular networks and effective drugs

Recent advances in the genomics of glioblastoma (GBM) led to the introduction of molecular neuropathology but failed to translate into treatment improvement. This is largely attributed to the genetic and phenotypic heterogeneity of GBM, which are considered the major obstacle to GBM therapy. Here, we use advanced human GBM organoid (LEGO: Laboratory Engineered Glioblastoma Organoid) and provide an unprecedented comprehensive characterization of LEGO models using single-cell transcriptome, DNA methylome, metabolome, lipidome, proteome, and phospho-proteome analysis. We discovered that genetic heterogeneity dictates functional heterogeneity across molecular layers and demonstrates that NF1 mutation drives mesenchymal signature. Most importantly, we found that glycerol lipid reprogramming is a hallmark of GBM, and several targets and drugs were discovered along this line. We also provide a genotype-based drug reference map using LEGO-based drug screen. This study provides novel human GBM models and a research path toward effective GBM therapy.

cancer biology↗

bioRxiv2023

Chiral Graphene Quantum Dots Enhanced Drug Loading into Exosomes

As nanoscale extracellular vesicles secreted by cells, exosomes have enormous potential as safe and effective vehicles to deliver drugs into lesion locations. Despite promising advances with exosome-based drug delivery systems, there are still challenges to drug loading into exosome, which hinder the clinical applications of exosomes. Herein, we report an exogenous drug-agnostic chiral graphene quantum dots (GQDs) exosome-loading platform, based on chirality matching with the exosome lipid bilayer. Both hydrophobic and hydrophilic chemical and biological drugs can be functionalized or adsorbed onto GQDs by {pi}-{pi} stacking and van der Waals interactions. By tuning the ligands and GQD size to optimize its chirality, we demonstrate drug loading efficiency of 66.3% and 64.1% for Doxorubicin and siRNA, which is significantly higher than other reported exosome loading techniques.

bioengineering↗

bioRxiv2023

Plasmodium falciparum GCN5 plays a key role in regulating artemisinin resistance-related stress responses

Plasmodium falciparum causes the most severe malaria and is exposed to various environmental and physiological stresses in the human host. Given that GCN5 plays a critical role in regulating stress responses in model organisms, we aimed to elucidate PfGCN5s function in stress responses in P. falciparum. The protein level of PfGCN5 was substantially induced under three stress conditions (heat shock, low glucose starvation, and dihydroartemisinin, the active metabolite of artemisinin (ART)). With a TetR-DOZI conditional knockdown (KD) system, we successfully down-regulated PfGCN5 to [~]50% and found that KD parasites became more sensitive to all three stress conditions. Transcriptomic analysis via RNA-seq identified [~]1,000 up-and down-regulated genes in the wildtype (WT) and KD parasites under these stress conditions. Importantly, DHA induced transcriptional alteration of many genes involved in many aspects of stress responses, which were heavily shared among the altered genes under heat shock and low glucose conditions, including ART-resistance-related genes such as K13 and coronin. Based on the expression pattern between WT and KD parasites under three stress conditions, [~]300-400 genes were identified to be involved in PfGCN5-dependent, general and stress-condition-specific responses with high levels of overlaps among three stress conditions. Notably, using ring-stage survival assay (RSA), we found that KD or inhibition of PfGCN5 could sensitize the ART-resistant parasites to the DHA treatment. All these indicate that PfGCN5 is pivotal in regulating general and ART-resistance-related stress responses in malaria parasites, implicating PfGCN5 as a potential target for malaria intervention. IMPORTANCEMalaria leads to about half a million deaths annually and these casualties were majorly caused by the infection of Plasmodium falciparum. This parasite strives to survive by defending against a variety of stress conditions, such as malaria cyclical fever (heat shock), starvation due to low blood sugar (glucose) levels (hypoglycemia), and drug treatment. Previous studies have revealed that P. falciparum has developed unique stress responses to different stresses including ART treatment, and ART-resistant parasites harbor elevated stress responses. In this study, we provide critical evidence on the role of PfGCN5, a histone modifier, and a chromatin coactivator, in regulating general and stress-specific responses in malaria parasites, indicating that PfGCN5 can be used as a potential target for anti-malaria intervention.

microbiology↗

bioRxiv2023

Spin-coupled electron densities of iron-sulfur cluster imaged by in situ serial Laue diffraction

Iron-sulfur clusters are inorganic cofactors found in many proteins involved in fundamental biological processes including DNA processing. The prokaryotic DNA repair enzyme PhrB, a member of the protein family of cryptochromes and photolyases, carries a four-iron-four-sulfur cluster [4Fe4S] in addition to the catalytic cofactor flavin adenine dinucleotide (FAD) and a second pigment 6,7-dimethyl-8-ribityllumazine (DMRL). The light-induced redox reactions of this multi-cofactor protein complex were recently shown as two interdependent photoreductions of FAD and DMRL mediated by the [4Fe4S] cluster functioning as an electron cache to hold a fine balance of electrons. Here, we apply the more traditional temperature-scan cryo-trapping technique in protein crystallography and the newly developed technology of in situ serial Laue diffraction at room temperature. These diffraction methods in dynamic crystallography enable us to capture strong signals of electron density changes in the [4Fe4S] cluster that depict quantized electronic movements. The mixed valence layers of the [4Fe4S] cluster due to spin coupling and their dynamic responses to light illumination are observed directly in our difference maps between its redox states. These direct observations of the quantum effects in a protein bound iron-sulfur cluster have thus opened a window into the mechanistic understanding of metal clusters in biological systems.

biophysics↗

bioRxiv2023

The "replacing surgery" of cpDNA: de novo chemical synthesis and in vivo functional testing of Chlamydomonas chloroplast genome

We have successfully designed and synthesized the 221,372-bp cpDNA SynCpV1.0 with the native cpDNA of Chlamydomonas reinhardtii as the template. Homoplasmic SynCpv1.0-harboring algal strains were obtained by biolistic transformation and selected with an ascending gradient of antibiotic pressure. Meanwhile, we were pleasantly surprised to find that SynCpV1.0 was able to re-introduce and replicate normally after the total DNA of transplastomic algal strains were transformed to Escherichia coli, it indicated that SynCpV1.0 was able to shuttle between C. reinhardtii and E. coli. Finally, we analyzed the photosynthetic properties of SynCpV1.0-harboring transplastomic strains, the results showed that they exhibited the same photosynthetic efficiency as the wild strain of C. reinhardtii CC125, and could rescue the photosynthetic defect in mutant strain of C. reinhardtii CC5168. Herein, we have performed the "replacing surgery" of cpDNA and established an ideal platform to complete multiple cycles of "Design-Build-Test" for optimizing the cpDNA of photosynthetic organisms. HighlightO_LIAn artificial cpDNA SynCpV1.0 is constructed by de novo chemical synthesis. C_LIO_LIThe "replacing surgery" of cpDNA was performed in the chloroplast of C. reinhardtii C_LIO_LIIt is found that artificial cpDNA was able to shuttle between Chlamydomonas chloroplast and E. coli. C_LIO_LIEstablish an ideal platform to complete multiple cycles of "Design-Build-Test" for optimizing the cpDNA. C_LI One-Sentence SummaryThe chloroplast genome can be replaced by a complete synthesized genome and performs the designed biological function in C. reinhardtii.

molecular biology↗

bioRxiv2023

Single-cell transcriptional analysis of lamina propria lymphocytes in the jejunum reveals ILC-like cells in pigs

Pigs are the most suitable model to study various therapeutic strategies and drugs for human beings, while knowledge about tissue- and cell-type-specific transcriptomes and heterogeneity is poorly available. Here, we focused on the intestinal immunity of pigs. Through single-cell sequencing (scRNA-seq) and flow cytometry analysis of the types of immune cells in the jejunum of pigs, we found that innate lymphoid cells (ILCs) existed in the lamina propria lymphocytes (LPLs) of the jejunum. Then, through flow sorting of Live/Dead (L/D)-Lineage(LIN)-CD45+ cells and scRNA-seq, we found that ILCs in the porcine jejunum were mainly ILC3s, with a small number of ILC1s, ILC2s, and NK cells. Through a gene expression map, we found that ILCs coexpressed IL-7R, ID2, and other genes and differentially expressed RORC, GATA3, and other genes but did not express the CD3 gene. According to their gene expression profiles, ILC3s can be divided into four subgroups, and genes such as CXCL8, CXCL2, IL-22, IL-17, and NCR2 are differentially expressed. To further detect and identify ILC3s, we prepared RORC monoclonal antibodies and verified the classification of ILCs in the porcine jejunum subgroup and the expression of related hallmark genes at the protein level by flow cytometry. For systematically characterizing of ILCs in the porcine intestines, we combined our pig ILCs dataset with publicly available human and mice ILCs data and identified that the humans and pigs ILCs shared more common features than those mice ILCs in gene signatures and cell states. For the first time, our results showed in detail the gene expression of porcine jejunal ILCs, the subtype classification of ILCs, and the markers of various ILCs, which provides a basis for an in-depth exploration of porcine intestinal mucosal immunity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/522424v3_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@184fd80org.highwire.dtl.DTLVardef@1efc00org.highwire.dtl.DTLVardef@328a04org.highwire.dtl.DTLVardef@3296e_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

immunology↗

bioRxiv2023

HERC5-catalyzed ISGylation potentiates cGAS-mediated innate immunity

The key cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) is essential to elicit anti-infection innate immunity whereas aberrant activation of cGAS by endogenous DNA promotes severe autoimmune diseases, thus the activity of cGAS must be strictly regulated to maintain immune homeostasis. Here we report that the E3 ISG15-protein ligase HERC5 interacts with and catalyzes the cGAS ISGylation robustly, whereas the deconjugating enzyme USP18 removes the ISG15 conjugation of cGAS. The interaction of cGAS and HERC5 depends on the cGAS N-terminal domain and the RRC1-4 and HECT domain of HERC5. Mass spectrometry reveals that the Lys21,187,219,458 are the potential ISGylation sites in human cGAS. Deficiency of ISG15 or the E1 ubiquitin-activating enzyme UBA7 greatly attenuate the downstream gene expression induced by cGAS-STING axis and the antiviral ability in mouse and human cells. Collectively, our study uncovered an important role of the HERC5-facilitated cGAS ISGylaion in promoting antiviral defense.

immunology↗

bioRxiv2022

Neurological Disorder after Severe Pneumonia is Associated with Translocation of Bacteria from Lung to Brain

The neurological disorder is a common feature in patients who recovered from severe acute pneumonia. However, the underline mechanisms remain not very clear. Here we show that these neurological syndromes after severe acute pneumonia are partly attributed to the translocation of bacteria from the lung to the brain during pneumonia. We detected an emerging and increased bacteria in the brain tissue of mice with lipopolysaccharide-induced experimental severe pneumonia. Interestingly, using 16S rDNA amplification sequencing, similarities were found between the brains flora species and those of the lungs, indicating the bacteria in the brain may originate from the lung. We also observed the impairment of the lung-blood barrier and brain-blood barrier, simultaneously, allowing lung bacteria invade the brain during pneumonia. An elevated microglia and astrocytes activation signature through bacterial infection-related pathways is observed by single-cell RNA sequencing, indicating a bacteria-induced disruption of brain homeostasis. Rapamycin delivered by platelet-derived extracellular vesicles provides an effective strategy to rescue the dysfunction of microglia and astrocytes, and relief neurological disorders. Collectively, we identify lung bacteria that play a role in altering brain homeostasis, which provides new insight into the mechanism of neurological syndromes after severe pneumonia.

neuroscience↗

bioRxiv2022

Lipoprotein sorting to the cell surface via a crosstalk between the Lpt and Lol pathways during outer membrane biogenesis

Lipopolysaccharide (LPS) and lipoprotein, two essential components of the outer membrane (OM) in Gram-negative bacteria, play critical roles in bacterial physiology and pathogenicity. LPS translocation to the OM is mediated by LptDE, yet how lipoproteins sort to the cell surface remains elusive. Here we report the identification of an inventory of lipoproteins that are transported to the cell surface via LptDE. Notably, we determined crystal structures of LptDE from Pseudomonas aeruginosa and its complex with an endogenous Escherichia coli lipoprotein YifL. The paLptDE-YifL structure demonstrates that YifL translocates to the OM via LptDE, in a manner similar to LPS transport. The {beta}-barrel domain serves as a passage for the proteinaceous moiety while its acyl chains are transported outside. Our finding has been corroborated by results from native mass spectrometry, immunofluorescence, and photocrosslinking assays, revealing a unique mechanism through which lipoproteins are translocated across the OM in an ATP- and LPS-dependent manner. Moreover, our study expands the scope of current knowledge of lipoprotein sorting by disclosing a crosstalk between the Lpt and Lol pathways.

microbiology↗

bioRxiv2022

MYSM1 co-activates ERα action via histone and non-histone deubiquitination to confer antiestrogen resistance in breast cancer

Endocrine resistance is a crucial challenge in estrogen receptor alpha (ER)-positive breast cancer (BCa) therapy. Aberrant alteration in modulation of E2/ER signaling pathway has emerged as the putative contributor for endocrine resistance in BCa. Thus, identification the efficient ER cofactor remains necessary for finding a potential therapeutic target for endocrine resistance. Herein, we have demonstrated that Myb like, SWIRM and MPN domains 1 (MYSM1) as a histone deubiquitinase is a novel ER co-activator with established Drosophila experimental model. Our results showed that MYSM1 participated in up-regulation of ER action via histone and non-histone deubiquitination. We provided the evidence to show that MYSM1 was involved in maintenance of ER stability via ER deubiquitination. Furthermore, silencing MYSM1 induced enhancement of histone H2A ubiquitination as well as reduction of histone H3K4me3 and H3Ac levels at cis regulatory elements on promoter of ER-regulated gene. In addition, MYSM1 depletion attenuated cell proliferation/growth in BCa-derived cell lines and xenograft models. Knockdown of MYSM1 increased the sensitivity of antiestrogen agents in BCa cells. MYSM1 was highly expressed in clinical BCa samples, especially in aromatase inhibitor (AI) non-responsive tissues. These findings clarify the molecular mechanism of MYSM1 as an epigenetic modifier in regulation of ER action and provide a potential therapeutic target for endocrine resistance in BCa.

cell biology↗

bioRxiv2022

ZBTB20 is Essential for Cochlear Maturation and Hearing in Mice

The mammalian cochlear epithelium undergoes substantial remodeling and maturation before the onset of hearing. However, very little is known about the transcriptional network governing cochlear late-stage maturation and particularly the differentiation of its lateral non-sensory region. Here we establish ZBTB20 as an essential transcription factor required for cochlear terminal differentiation and maturation and hearing. ZBTB20 is abundantly expressed in the developing and mature cochlear non-sensory epithelial cells, with transient expression in immature hair cells and spiral ganglion neurons. Otocyst-specific deletion of Zbtb20 causes profound deafness with reduced endolymph potential in mice. The subtypes of cochlear epithelial cells are normally generated but their postnatal development is arrested in the absence of ZBTB20, as manifested by an immature appearance of the organ of Corti, malformation of tectorial membrane, a flattened spiral prominence, and a lack of identifiable Boettcher cells. Furthermore, these defects are related with a failure in the terminal differentiation of the non-sensory epithelium covering the outer border Claudius cells, outer sulcus root cells and spiral prominence epithelial cells. Transcriptome analysis shows ZBTB20 regulates genes coding for tectorial membrane proteins in the greater epithelial ridge, and those preferentially expressed in root cells and spiral prominence epithelium. Our results point to ZBTB20 as an essential regulator for postnatal cochlear maturation and particularly for the terminal differentiation of cochlear lateral non-sensory domain.

developmental biology↗

bioRxiv2022

The structural basis of itch receptor MRGPRX1 activation

Mas-related G-protein-coupled receptors X1-X4 (MRGPRX1-X4) are four primate-specific receptors that are recently reported to be responsible for many biological processes, including itch sensation, pain transmission, and inflammatory reactions. MRGPRX1 is the first identified human MRGPR, and its expression is restricted to primary sensory neurons. Due to its dual roles in itch and pain signaling pathways, MRGPRX1 has been regarded as a promising target for itch remission and pain inhibition. Here, we reported a cryo-electron microscopy (cryo-EM) structure of Gq-coupled MRGPRX1 in complex with a synthetic agonist compound 16 in an active conformation at an overall resolution of 3.0 angstrom via a NanoBiT tethering strategy. Compound 16 is a new pain-relieving compound with high potency and selectivity to MRGPRX1 over opioid receptor. According to the structure analysis, we revealed that MRGPRX1 shares common features of the Gq-mediated receptor activation mechanism of MRGPRX family members. However, the variable residues in orthosteric pocket of MRGPRX1 exhibits the unique agonist recognition pattern, which may facilitate to design MRGPRX1-specific modulators. Together with receptor activation and itch behavior evaluation assays, our study provides a structural snapshot to modify therapeutic molecules for itch relieving and analgesia targeting MRGPRX1.

biochemistry↗

bioRxiv2022

Polyethylene valorization by combined chemical catalysis with bioconversion by plastic-enriched microbial consortia

There are few reports of microbial deconstruction or functionalization of the recalcitrant backbone of polyolefins. However, microbes can utilize polyolefin deconstruction products, including n-alkanes. Here, we combined chemical catalysis with bioconversion to valorize polyethylene (PE) deconstruction products. High-density PE (HDPE) was deconstructed via hydrogenolysis over a ruthenium on carbon catalyst. The resulting n-alkane mixture (C4-C35) was utilized as a feedstock for microbial consortia derived from soil from local recycling plants. We found two consortia that utilized the PE-deconstruction product mix as a sole carbon source. We adapted the consortia on a commercially-available n-alkane mix to reduce the number of species present and enrich for enhanced alkane utilization. Both resulting enriched consortia utilized the PE-deconstruction product mix more effectively than the original (parent) consortia. The predominant metabolite produced by both enriched consortia was a C16-C16 wax ester. Wax esters have considerable industrial value, with the longer chain lengths (C32-C36) having the highest value. We identified two Rhodococcus aetherivorans strains that grow well on C24, indicating this species is important for the functionalization of long-chain alkanes. This work demonstrates that enriched consortia from plastic-enriched environments can be combined with chemical catalysis to valorize polyethylene. SynopsisChemical catalysis can be used to deconstruct polyethylene waste material to produce a mixture of alkanes. Enriched environmental microbial consortia can valorize these polyethylene deconstruction products via functionalization that preserves the alkane chain length thus minimizing CO2 production.

bioengineering↗

bioRxiv2022

An important role for triglyceride in regulating spermatogenesis

Drosophila is a powerful model to study how lipids affect spermatogenesis. Yet, the contribution of neutral lipids, a major lipid group which resides in organelles called lipid droplets (LD), to sperm development is largely unknown. Emerging evidence suggests LD are present in the testis and that loss of neutral lipid- and LD-associated genes causes subfertility; however, key regulators of testis neutral lipids and LD remain unclear. Here, we show LD are present in early-stage somatic and germline cells within the Drosophila testis. We identified a role for triglyceride lipase brummer (bmm) in regulating testis LD, and found that whole-body loss of bmm leads to defects in sperm development. Importantly, these represent cell-autonomous roles for bmm in regulating testis LD and spermatogenesis. Because lipidomic analysis of bmm mutants revealed excess triglyceride accumulation, and spermatogenic defects in bmm mutants were rescued by genetically blocking triglyceride synthesis, our data suggest that bmm-mediated regulation of triglyceride influences sperm development. This identifies triglyceride as an important neutral lipid that contributes to Drosophila sperm development, and reveals a key role for bmm in regulating testis triglyceride levels during spermatogenesis.

developmental biology↗

bioRxiv2022

STING-dependent cytosolic DNA sensing pathway drives the progression to leukemia in TET2-mutated HSPCs

Somatic loss-of-function mutations of the dioxygenase Ten-eleven translocation-2 (TET2) occur frequently in individuals with clonal hematopoiesis (CH) and acute myeloid leukemia (AML). These common hematopoietic disorders can be recapitulated in mouse models. However, the underlying mechanisms by which the deficiency in TET2 promotes these disorders remain largely unknown. Here we show that the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway is activated to mediate the effect of TET2 deficiency in leukemogenesis in mouse models. DNA damage arising in Tet2-deficient hematopoietic stem/progenitor cells (HSPCs) leads to activation of the cGAS-STING pathway which in turn induces the development of CH and myeloid transformation. Notably, both pharmacological inhibition and genetic deletion of STING suppresses Tet2 mutation-induced aberrant myelopoiesis. In patient-derived xenograft (PDX) models, STING inhibition specifically attenuates the proliferation of leukemia cells from TET2-mutated individuals. These observations suggest that the hematopoietic transformation associated with TET2 mutations is powered through sterile inflammation dependent on the activated cGAS-STING pathway, and that STING may represent a potential target for intervention of relevant hematopoietic malignancies. Key pointsO_LITet2 deficiency leads to DNA damage which in turn activates the cGAS-STING pathway to induce an inflammatory response C_LIO_LIBlocking STING in TET2-mutated hematopoietic stem/progenitor cells suppresses clonal hematopoiesis in mice and leukemogenesis in patient-derived xenograft models C_LI

cancer biology↗

bioRxiv2022

Enhancer-driven gene regulatory networks inference from single-cell RNA-seq and ATAC-seq data

Deciphering the intricate relationships between transcription factors (TFs), enhancers, and genes through the inference of enhancer-driven gene regulatory networks is crucial in understanding gene regulatory programs in a complex biological system. This study introduces STREAM, a novel method that leverages a Steiner Forest Problem model, a hybrid biclustering pipeline, and submodular optimization to infer enhancer-driven gene regulatory networks from jointly profiled single-cell transcriptome and chromatin accessibility data. Compared to existing methods, STREAM demonstrates enhanced performance in terms of TF recovery, TF-enhancer relation prediction, and enhancer-gene discovery. Application of STREAM to an Alzheimers disease dataset and a diffuse small lymphocytic lymphoma dataset reveals its ability to identify TF-enhancer-gene relationships associated with pseudotime, as well as key TF-enhancer-gene relationships and TF cooperation underlying tumor cells.

bioinformatics↗

bioRxiv2022

Latitude influences stability via stabilizing mechanisms in naturally-assembled forest ecosystems at different spatial grains

Ecosystem stability reveals how ecosystems respond to global change over time. Yet, the focus of past research on small spatial grains and extents overlooks scale dependence and how broad-scale environmental gradients shape stability. Here, we use forest inventory data covering a broad latitudinal gradient from the temperate to the tropical zone to examine cross-scale variation in stability of aboveground biomass and underlying stabilizing mechanisms. While stability did not shift systematically with latitude at either spatial grain, we found evidence that species asynchrony increased towards the tropics at the small spatial grain while species stability decreased at both spatial grains. Moreover, latitude stabilized forest communities via its effects on both stabilizing mechanisms, which compensated for the weak and destabilizing effects of species richness. Yet, the trade-off in the relative importance of species stability and species asynchrony for stability was not mediated by latitude, suggesting that context-dependent factors - to a greater extent than macroecological ones - underlie large-scale patterns of stability. Our results highlight the crucial role of species asynchrony and species stability in determining ecosystem stability across broad-scale environmental gradients, suggesting that conserving biodiversity alone may not be sufficient for stabilizing naturally-assembled forest ecosystems.

ecology↗