Biology subjects

Tang, Y.

Publications and source records attributed to Tang, Y..

At least 271 records · Page 15Linked to original sources

bioRxiv2020

Proinflammatory S100A9 Regulate Differentiation and Aggregation of Neural Stem Cells

Inflammation is the primary pathological feature of neurodegenerative diseases such as Alzheimers (AD) and Parkinsons disease. Proinflammatory molecules (e.g. S100A9) play important roles during progression of the diseases by regulating behavior and fate of multiple cell types in the nervous system (1). Our earlier studies reveal that S100A9 is toxic to neurons, and its interaction with A{beta} peptides leads to the formation of large non-toxic amyloidogenic aggregates, suggesting a protective role of A{beta} amyloids (2). We herein, demonstrate that S100A9 interacts with neural stem cells (NSCs) and causes NSC differentiation. In the brain of transgenic AD mouse models, we found large quantities of proinflammatory S100A9, which colocalizes with the differentiated NSCs. NSC sphere formation, which is a representative character of NSC stemness, is also substantially inhibited by S100A9. These results suggest that S100A9 is a representative marker for the inflammatory conditions in AD, and it promotes NSC differentiation. Intriguingly, in contrast to the death of both stem and differentiated NSCs caused by high S100A9 doses, S100A9 at a moderate concentration is toxic only to the early differentiated NSCs (i.e. progenitor cells and immature neurons), but not the stem cells. We therefore postulate that at the early stage of AD, expression of S100A9 leads to NSC differentiation, which remedies the neuron damages. The application drugs, which help maintain NSC stemness (e.g. PDGF), may help overcome the acute inflammatory conditions and improve the efficacy of NSC transplantation therapy.

cell biology↗

bioRxiv2020

CaaX-like protease of cyanobacterial origin is required for complex plastid biogenesis in malaria parasites

Plasmodium parasites and related apicomplexans contain an essential "complex plastid" organelle of secondary endosymbiotic origin, the apicoplast. Biogenesis of this complex plastid poses a unique challenge requiring evolution of new cellular machinery. We previously conducted a mutagenesis screen for essential apicoplast biogenesis genes to discover organellar pathways with evolutionary and biomedical significance. Here we validate and characterize a gene candidate from our screen, Pf3D7_0913500. Using a conditional knockdown strain, we show that Pf3D7_0913500 depletion causes growth inhibition that is rescued by the sole essential product of the apicoplast, isopentenyl pyrophosphate (IPP), and results in apicoplast loss. Because Pf3D7_0913500 had no previous functional annotation, we name it apicoplast-minus IPP-rescued 4 (AMR4). AMR4 has an annotated CaaX Protease and Bacteriocin Processing (CPBP) domain, which in eukaryotes typically indicates a role in CaaX post-prenylation processing. Indeed, AMR4 is the only CaaX-like protease in Plasmodium parasites which are known to require protein prenylation, and we confirm that the conserved catalytic residue of AMR4 is required for its apicoplast function. However, we unexpectedly find that AMR4 does not act in a CaaX post-prenylation processing pathway in P. falciparum. Instead, we find that AMR4 is imported into the apicoplast and is derived from a cyanobacterial CPBP gene which was retained through both primary and secondary endosymbiosis. Our findings suggest that AMR4 is not a true CaaX protease, but instead acts in a conserved, uncharacterized chloroplast pathway that has been retained for complex plastid biogenesis. ImportancePlasmodium parasites, which cause malaria, and related apicomplexans are important human and veterinary pathogens. These parasites represent a highly divergent and understudied branch of eukaryotes, and as such often defy the expectations set by model organisms. One striking example of unique apicomplexan biology is the apicoplast, an essential but non-photosynthetic plastid derived from an unusual secondary (eukaryote-eukaryote) endosymbiosis. Endosymbioses are a major driver of cellular innovation, and apicoplast biogenesis pathways represent a hotspot for molecular evolution. We previously conducted an unbiased screen for apicoplast biogenesis genes in P. falciparum to uncover these essential and innovative pathways. Here, we validate a novel gene candidate from our screen and show that its role in apicoplast biogenesis does not match its functional annotation predicted by model eukaryotes. Our findings suggest that an uncharacterized chloroplast maintenance pathway has been reused for complex plastid biogenesis in this divergent branch of pathogens.

cell biology↗

bioRxiv2020

SLE non-coding Genetic Risk Variant Determines the Epigenetic Dysfunction of an Immune Cell Specific Enhancer that Controls Disease-critical microRNA Expression

The human genome contains millions of putative regulatory elements, which regulate gene expression. We are just beginning to understand the functional consequences of genetic variation within these regulatory elements. Since the bulk of common genetic variation impacting polygenic disease phenotypes localizes to these non-coding regions of the genome, understanding the consequences will improve our understanding of the mechanisms mediating genetic risk in human disease. Here, we define the systemic lupus erythematosus (SLE) risk variant rs2431369 as likely causal for SLE and show that it is located in a functional regulatory element that modulates miR-146a expression. We use epigenomic analysis and genome-editing to show that the rs2431697-containing region is a distal enhancer that specifically regulates miR-146a expression in a cell-type dependent manner. 3D chromatin structure analysis demonstrates physical interaction between the rs2431697-containing region and the miR-146a promoter. Further, our data show that NF-kB binds the disease protective allele in a sequence-specific manner, leading to increased expression of this immunoregulatory microRNA. Our work provides a strategy for using disease-associated variants to define the functional regulatory elements of non-coding RNA molecules such as miR-146a and provides mechanistic links between autoimmune disease risk genetic variation and disease etiology.

genetics↗

bioRxiv2020

Modeling the dynamics of antibody-target binding in living tumors

Antibodies have become an attractive class of therapeutic agents for solid tumors, mainly because of their high target selectivity and affinity. The target binding properties of antibodies are critical for their efficacy and toxicity. Our lab has developed a bioluminescence resonance energy transfer (BRET) imaging approach that directly supports measurement of the binding dynamics between antibodies and their targets in the native tumor environment. In the present study, we have developed a spatially resolved computational model to analyze the longitudinal BRET imaging of antibody-target binding and to explore the mechanisms of biphasic binding dynamics between cetuximab and its target, the epidermal growth factor receptor (EGFR). The model suggested that cetuximab bound differently to EGFR in the stroma-rich area than in stroma-poor regions, and this difference was confirmed by immunofluorescence staining. Compared to the binding in vitro, cetuximab bound to EGFR to a "slower-but-tighter" degree in the living tumors. These findings have provided spatially resolved characterizations of antibody-target binding in living tumors and have yielded many mechanistic insights into the factors that affect antibody interactions with its targets.

pharmacology and toxicology↗

bioRxiv2020

Quantitatively Modeling Factors that Influence the Therapeutic Doses of Antibodies

Dose selection and confirmation are critical tasks in the development of therapeutic antibodies. These tasks could become particularly challenging in the absence of robust pharmacodynamics biomarkers or at very flat dose-response curves. Although much knowledge has been acquired in the past decade, it remains uncertain which factors are relevant and how to select doses more rationally. In this study, we developed a quantitative metric, Therapeutic Exposure Affinity Ratio (TEAR), to retrospectively evaluate up to 60 approved antibodies and their therapeutic doses (TDs), and systematically assessed the factors that are relevant to antibody TDs and dose selection patterns. This metric supported us to analyze many factors that are beyond antibody pharmacokinetics and target binding affinity. Our results challenged the traditional perceptions about the importance of target turnovers and target anatomical locations in the selection of TDs, highlighted the relevance of an overlooked factor, antibody mechanisms of action. Overall, this study provided insights into antibody dose selection and confirmation in the development of therapeutic antibodies.

pharmacology and toxicology↗

bioRxiv2020

An Arf/Rab cascade controls the growth and invasiveness of glioblastoma

Glioblastoma is the most common and deadly malignant brain cancer. We now demonstrate that loss of function of the endosomal GTPase Rab35 in human brain tumor initiating cells (BTICs) increases glioblastoma growth and decreases animal survival following BTIC implantation in mouse brain. Mechanistically, we identify that the GTPase Arf5 interacts with the guanine nucleotide exchange factor (GEF) for Rab35, DENND1/connecdenn and allosterically enhances its GEF activity towards Rab35. Knockdown of either Rab35 or Arf5 increases cell migration, invasiveness and self-renewal in culture and enhances the growth and invasiveness of BTIC-initiated brain tumors in mice. RNAseq of the tumors reveals upregulation of the tumor-promoting transcription factor SPOCD1, and disruption of the Arf5/Rab35 axis in glioblastoma cells leads to strong activation of the epidermal growth factor receptor with resulting enhancement of SPOCD1 levels. These discoveries reveal an unexpected cascade between an Arf and a Rab and indicate a role for the cascade, and thus endosomal trafficking, in brain tumors.

cancer biology↗

bioRxiv2020

Conformational Selection in Ligand Recognition by the First Tudor Domain of PHF20L1

The first Tudor domain of PHF20L1 (PHF20L1 Tudor1) recognizes both histone methylation and non-histone methylation to play versatile roles, e.g., PHF20L1 Tudor1 binds to the oncogenic target DNA (cytosine-5) methyltransferase 1 (DNMT1) to prevent it from degradation. However, the crystal structure of the PHF20 Tudor domain, a homolog of PHF20L1, reveals a closed aromatic cage of the Tudor domain. It is thus highly desirable to interrogate the ligand-recognition mechanism of PHF20L1 Tudor1, which will in turn validate the potential druggability of this target. Here, we solved the crystal structure of the free form PHF20L1 Tudor1, which adopts the closed conformation similar to PHF20. NMR relaxation dispersion and molecular dynamics (MD) simulations suggest a pre-existing low-population conformation with a remarkable rearrangement of aromatic cage residues. Such structural rearrangement is further revealed by the crystal structures of PHF20L1 Tudor1 in complex with the lysine 142 methylated (K142me1) DNMT1, and a small molecule cosolvent 2-(N-morpholino)ethanesulfonic acid (MES), respectively. This result thus ignites interest in the discovery of small molecule inhibitors against PHF20L1 Tudor1. The hit identified from NMR fragment-based screening protrudes into the same open form aromatic cage of PHF20L1 Tudor1, and blocks the interaction between PHF20L1 Tudor1 and methylated DNMT1. Further free form crystal structures of key mutants reveal one open form and one closed form aromatic cage, which is energetically trapped observed in the NMR relaxation dispersion and MD simulations. The binding of DNMT1 with PHF20L1 Tudor1 mutants was also recapitulated in cancer cells. The mutagenesis thus alters the structure, dynamics and eventually the function of PHF20L1 Tudor1. Our results demonstrate that PHF20L1 Tudor1 utilizes the same conformational selection mechanism to recognize ligands, regardless of whether it is a natural substrate or a small molecule identified from fragment-based screening. Albeit at a low population, the pre-existing ligand-binding conformation shall shift the paradigm in the druggability assessment of a dynamic protein, even though it may lack a small molecule binding pocket in its free form structure. The inhibition of PHF20L1 paves an alternative way to target DNMT1 degradation.

biochemistry↗

bioRxiv2020

An incoherent feedforward loop interprets NFκB/RelA dynamics to determine TNF-induced necroptosis decisions

Balancing cell death is essential to maintain healthy tissue homeostasis and prevent disease. Tumor necrosis factor (TNF) not only activates nuclear factor {kappa}B (NF{kappa}B), which coordinates the cellular response to inflammation, but may also trigger necroptosis, a pro-inflammatory form of cell death. Whether TNF-induced NF{kappa}B cross-regulates TNF-induced necroptosis fate decisions is unclear. Live-cell microscopy and model-aided analysis of death kinetics identified a molecular circuit that interprets TNF-induced NF{kappa}B/RelA dynamics to control necroptosis decisions. Inducible expression of TNFAIP3/A20 forms an incoherent feedforward loop to interfere with the RIPK3-containing necrosome complex and protect a fraction of cells from transient, but not long-term TNF exposure. Furthermore, dysregulated NF{kappa}B dynamics often associated with disease diminish TNF-induced necroptosis. Our results suggest that TNFs dual roles in either coordinating cellular responses to inflammation, or further amplifying inflammation are determined by a dynamic NF{kappa}B-A20-RIPK3 circuit, that could be targeted to treat inflammation and cancer.

systems biology↗

bioRxiv2020

Resolving an underrepresented circulating tumor cell population in lung cancer enabled by Hexokinase 2 analysis

Unlike other epithelial cancer types, circulating tumor cells (CTCs) are less frequently detected in the peripheral blood of non-small cell lung cancer (NSCLC) patients using epithelial marker-based detection approaches, despite the aggressive nature of NSCLC. Here we demonstrate hexokinase-2 (HK2) as a metabolic function-associated marker for detection of CTCs, with significantly improved detection rates and high specificity, in 33 NSCLC patients. Use of the HK2 marker identified underrepresented cytokeratin-negative (HK2high/CKneg) CTCs present in many blood samples but rarely detected in pleural effusions or cerebrospinal fluids of NSCLC patients. HK2high/CKneg CTCs exhibited smaller sizes but consistent copy number variation profiles compared to CKpos CTCs. Surprisingly, CK expression levels were found to be independent of CTC epithelial-to-mesenchymal transition (EMT) status as measured by single-cell transcriptome profiling, challenging the long-standing association between CK expression and EMT. Our approach improves sensitivity of CTC detection in NSCLC and can potentially resolve a more complete spectrum of CTCs, regardless of their CK expression levels or epithelial traits.

cancer biology↗

bioRxiv2020

Development of a Novel Class of Self-Assembling dsRNA Cancer Therapeutics: a Proof of Concept Investigation

Cancer has proven to be an extremely difficult challenge to treat. Several fundamental issues currently underlie cancer treatment including differentiating self from non-self, functional coupling of the recognition and therapeutic components of various therapies, and the propensity of cancerous cells to develop resistance to common treatment modalities via evolutionary pressure. Given these limitations, there is an increasing need to develop an all-encompassing therapeutic that can uniquely target malignant cells, decouple recognition from treatment, and overcome evolutionarily driven cancer resistance. We describe herein, a new class of programmable self-assembling dsRNA-based cancer therapeutics, that uniquely targets aberrant genetic sequences, and in a functionally decoupled manner, undergoes oncogenic RNA activated displacement (ORAD), initiating a therapeutic cascade that induces apoptosis and immune activation. As a proof-of-concept, we show that RNA strands targeting the EWS/Fli1 fusion gene in Ewing Sarcoma cells that are end-blocked with phosphorothioate bonds and additionally sealed with a 2-U modified DNA protector can be used to induce specific and potent killing of cells containing the target oncogenic sequence, but not wildtype.

bioengineering↗

bioRxiv2020

Dietary supplementation with products of Citrus reticulata "Chachi" for improving the fecal microbiome of weaned piglets

Nutritional interventions play a critical role in modifying the intestinal microbiome of host animals. This study was conducted to interrogate the physiological effects on fecal microflora of weaned piglets via the dietary supplemented with two types of products of Citrus reticulata "Chachi", respectively. For this purpose, A total of 72 piglets with uniform sizes were randomly assigned to four dietary treatment groups consisted of a negative control group (NCG), a fermented citrus reticulata "Chachi" pulp group (FCRPG), a Citri Reticulatae Pericarpium group (CRPG) and a positive control group (PCG) in a 21-day feeding trial. After the raising experiment, fresh feces of piglets were analyzed systematically using multi-omics technologies. Metagenomics method with high-throughput compositional characterization indicated that the architecture and diversity of fecal microbiome were both influenced by these two additives and compound antibiotics. Metabolite analysis showed that FCRPG have an significant effects on fecal short-chain fatty acids (SCFAs) among four treatment groups. Results of functional proteomics approaches found that FCRPG presented the highest butyrate metabolic level, and CRPG showed the highest flavone and flavonol biosynthesis level in feces. In addition, NCP produced an effective effect on adjusting fecal microbiota profile. Consequently, our findings demonstrate that dietary supplementation with FCRP or CRP modulates the microbial taxa, metabolic and proteomic alterations in fecal microbiota of weaned piglets for health maintaining.

microbiology↗

bioRxiv2020

Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity that may underly population disparities in this disease

Systemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underly the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertook a genome-wide association study, increasing the sample size of Chinese populations to the level of existing European studies. Thirty-eight novel SLE-associated loci and incomplete sharing of genetic architecture were identified. Nine disease loci showed clear ancestral group heterogeneity and implicated antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores performed significantly better when trained on matched ancestral data sets. These analyses help to reveal the genetic bases for disparities in SLE among ancestral groups.

genetics↗

bioRxiv2020

Comparative morphological and transcriptomic analyses reveal novel chemosensory genes in the poultry red mite, Dermanyssus gallinae and knockdown by RNA interference

Detection of chemical cues via chemosensory receptor proteins are essential for most animals, and underlies critical behaviors, including location and discrimination of food resources, identification of sexual partners and avoidance of predators. The current knowledge of how chemical cues are detected is based primarily on data acquired from studies on insects, while our understanding of the molecular basis for chemoreception in acari, mites in particular, remains limited. The poultry red mite (PRM), Dermanyssus gallinae, is one of the most important blood-feeding ectoparasites of poultry. Unlike other ectoparasites on animals, PRM feeds mainly at night. During daytime, these animals hide themselves in crevices around the poultry house. The diversity in habitat usage, as well as the demonstrated host finding and avoidance behaviors suggest that PRM relies on their sense of smell to orchestrate complex behavioral decisions. Comparative transcriptome analyses revealed the presence of candidate variant ionotropic receptors (IRs), odorant binding proteins (OBPs), niemann-pick proteins type C2 (NPC2) and sensory neuron membrane proteins (SNMPs). Some of these proteins were highly and differentially expressed in the forelegs of PRM. Rhodopsin-like G protein-coupled receptors (GPCRs) were also identified, while insect-specific odorant receptors (ORs) and odorant co-receptors (ORcos) were not detected. Furthermore, using scanning electron microscopy (SEM), the tarsomeres of all legs pairs were shown to be equipped with sensilla chaetica with or without tip pores, while wall-pored olfactory sensilla chaetica were restricted to the distal-most tarsomeres of the forelegs. Further, using the conserved odorant binding protein (OBP) as a test case, the results showed that RNA interference (RNAi) can be induced in D. gallinae chemosensory tissues. This study is the first to describe the presence of chemosensory genes in any Dermanyssidae family. It is also the first report of chemosensory gene knockdown by RNAi in any mite species and demonstrate that their diminutive size, less than 1 mm, is not a major impediment when applying gene knockdown approaches. Our findings make a significant step forward in understanding the chemosensory abilities of D. gallinae.

molecular biology↗

bioRxiv2020

Identification and exploration of 2'-O-methylation sites in rRNA and mRNA with a novel RNase based platform

Ribose 2'-O-methylation is involved in critical biological processes, but its biological functions and significance in mRNAs remain largely unknown due to the lack of accurate and efficient identification tools. To overcome this gap, we established NJU-seq (an accurate high-throughput single-base method) and Nm-VAQ (a site-specific quantification tool). We identified thousands of new Nm sites on mRNA of human and mouse cell lines, in which 68 of 84 selected sites were further validated to be 2'-O-methylated more than 1%. Unlike rRNA, the methylated ratios of most validated mRNA Nm sites were lower than 30%. In addition, mRNA 2'-O-methylation was dynamic-changing according to the circumstance, which was presented with MHV infection. Furthermore, Nm sites of lung surgery samples revealed commonness of lung cancer pathogenesis, providing potential new diagnostic markers.

biochemistry↗

bioRxiv2020

The effects of human umbilical cord mesenchymal stem cell transplantation on female fertility preservation in mice

Female fertility is the capacity to produce oocytes and achieve fertilization and pregnancy, and these outcomes are impaired by age, diseases, environment and social pressure. However, there is no effective therapy that preserves female reproductive ability. Mesenchymal stromal cells (MSCs) can exhibit multidirectional differentiation potential, and they have gained great attention as a tool for preserving female fertility. Therefore, this study uses human umbilical cords-MSCs (Huc-MSCs) to preserve and restore fertility in aging female mice and chemotherapy-damaged mice through the rescue of ovarian function and the reconstruction of the fallopian tubes and uterus. In our study, 2 mouse models were generated: aging mice (37 weeks old) and chemotherapy-damaged mice. Then, we injected Huc-MSCs into mice through the tail vein. After treatment, the effect of MSCs on the ovary, fallopian tubes and uterus was evaluated by analyzing gonadal hormone levels and by performing morphological analysis and statistical analysis. The levels of E2 and FSH exhibited a significant recovery after HUC-MSC transplantation both in aging mice and mice treated with chemotherapy. Huc-MSC treatment also increased the numbers of primordial, developing and preovulatory follicles in the ovaries of mice. Meanwhile, MSCs have been shown to rescue the morphology of the fallopian tubes and uterus through mechanisms such as regenerating the cilia in fallopian tubes and reforming glands and chorionic villi in the uterus. Therefore, it is suggested that Huc-MSCs may represent an effective potential treatment for preserving female fertility through recovery from chemotherapy damage and rescuing female reproductive organs from the effects of aging.

cell biology↗

bioRxiv2020

Functional modeling of NMIHBA-causing PRUNE1 variants reveals a requirement for its exopolyphosphatase activity.

Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA) is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by global developmental delay and severe intellectual disability. Microcephaly, progressive cortical atrophy, cerebellar hypoplasia and delayed myelination are neurological hallmarks in affected individuals. NMIHBA is caused by biallelic variants in PRUNE1 encoding prune exopolyphosphatase 1. We provide in-depth clinical description of two affected siblings harboring compound heterozygous variant alleles, c.383G>A (p.Arg128Gln), c.520G>T (p.Gly174*) in PRUNE1. To gain insights into disease biology, we biochemically characterized missense variants within the conserved N-terminal aspartic acid-histidine-histidine (DHH) motif and provide evidence that they result in the destabilization of protein structure and/or loss of exopolyphosphatase activity. Genetic ablation of Prune1 results in midgestational lethality in mice, associated with perturbations to embryonic growth and vascular development. Our findings suggest that NMIHBA results from hypomorphic variant alleles in humans and underscore the potential key role of PRUNE1 exopolyphoshatase activity in neurodevelopment.

genetics↗

bioRxiv2020

Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells

The derivation of self-renewing tissue-specific stem cells from human induced pluripotent stem cells (iPSCs) would shorten the time needed to engineer mature cell types in vitro and would have broad reaching implications for the field of regenerative medicine. Here we report the directed differentiation of human iPSCs into putative airway basal cells ("iBCs"), a population resembling the epithelial stem cell of lung airways. Using a dual fluorescent reporter system (NKX2-1GFP;TP63tdTomato) we track and purify these cells over time, as they first emerge from iPSC-derived foregut endoderm as developmentally immature NKX2-1GFP+ lung progenitors which then augment a TP63 program during subsequent proximal airway epithelial patterning. These cells clonally proliferate, initially as NKX2-1GFP+/TP63tdTomato+ immature airway progenitors that lack expression of the adult basal cell surface marker NGFR. However, in response to primary basal cell medium, NKX2-1GFP+/ TP63tdTomato+ cells upregulate NGFR and display the molecular and functional phenotype of airway basal stem cells, including the capacity to clonally self-renew or undergo multilineage ciliated and secretory epithelial differentiation in air-liquid interface cultures. iBCs and their differentiated progeny recapitulate several fundamental physiologic features of normal primary airway epithelial cells and model perturbations that characterize acquired and genetic airway diseases. In an asthma model of mucus metaplasia, the inflammatory cytokine IL-13 induced an increase in MUC5AC+ cells similar to primary cells. CFTR-dependent chloride flux in airway epithelium generated from cystic fibrosis iBCs or their syngeneic CFTR-corrected controls exhibited a pattern consistent with the flux measured in primary diseased and normal human airway epithelium, respectively. Finally, multiciliated cells generated from an individual with primary ciliary dyskinesia recapitulated the ciliary beat and ultrastructural defects observed in the donor. Thus, we demonstrate the successful de novo generation of a tissue-resident stem cell-like population in vitro from iPSCs, an approach which should facilitate disease modeling and future regenerative therapies for a variety of diseases affecting the lung airways.

developmental biology↗

bioRxiv2020

A systematic review of scientific research focused on farmers in agricultural adaptation to climate change (2008-2017)

Due to the severe consequences of climate change, associated risks to global food security, and the contribution of agriculture to greenhouse gas emissions, agriculture must necessarily adapt to meet these challenges. Many studies have therefore sought to investigate agricultural adaptation to climate change, and as key stakeholders in agriculture, farmers play a vital role in this process. There is a rapidly increasing corpus of scholarship on agricultural adaptation to climate change, with many studies beginning to incorporate survey methods to examine farmer perceptions and adaptation responses. Nevertheless, in-depth understanding of farmers worldwide is inadequate due to insufficiently robust methodologies, socio-economic disparities, and unequal geographic distribution. In this study, we searched and reviewed the existing peer-reviewed, English-language scientific articles published between 2008 and 2017 on agricultural adaptation to climate change that have incorporated farmers into their research methodologies. The main findings include the following: (1) a small but increasing number of studies focus on farmers in climate change adaptation; (2) the global geographic distribution of the reviewed studies is uneven, and many of the most vulnerable nations (e.g., lower-income/agricultural-dependent economies) have no representation at all; (3) there were diverse rationales and methods for incorporating farmers into the studies, and many of the methodological differences were due to practical and logistical limitations in lower-income/agricultural-dependent nations; and (4) studies were from multiple academic fields, indicating the need for more interdisciplinary collaboration moving forward because agricultural adaptation to climate change is too complex for a single discipline to fully explore. Although English is increasingly recognized as the "international language of science," due to the challenge of language segmentation limiting broader understanding of global scholarship whenever possible, future reviews should be jointly conducted in both English and non-English languages.

scientific communication and education↗