Biology subjects

Han, F.

Publications and source records attributed to Han, F..

46 records · Page 3Linked to original sources

bioRxiv2020

Proto-sex locus in large yellow croaker provides insights into early evolution of the sex chromosome

Autosomal origins of heterogametic sex chromosomes have been inferred frequently from suppressed recombination and gene degeneration manifested in incompletely differentiated sex chromosomes. However, the initial transition of an autosome region to a proto-sex locus has been not explored in depth. By assembling and analyzing a chromosome-level draft genome, we found a recent (evolved 0.26 million years ago), highly homologous, and dmrt1 containing sex-determination locus with slightly reduced recombination in large yellow croaker (Larimichthys crocea), a teleost species with genetic sex determination (GSD) and with undifferentiated sex chromosomes. We observed genomic homology and polymorphic segregation of the proto-sex locus between sexes. Expression of dmrt1 showed a stepwise increase in the development of testis, but not in the ovary. We infer that the inception of the proto-sex locus involves a few divergences in nucleotide sequences and slight suppression of recombination in an autosome region. In androgen-induced sex reversal of genetic females, in addition to dmrt1, genes in the conserved dmrt1 cluster, and the rest of the sex determination network were activated. We provided evidence that broad functional links were shared by genetic sex determination and environmental sex reversal.

evolutionary biology↗

bioRxiv2020

The coupling of global brain activity and cerebrospinal fluid inflow is correlated with Alzheimer's disease related pathology

The glymphatic system plays an important role in clearing the amyloid-{beta} and tau proteins that are closely linked to Alzheimers disease (AD) pathology. Glymphatic clearance, as well as amyloid-{beta} accumulation, is highly dependent on sleep, but the sleep-dependent driving forces behind cerebrospinal fluid (CSF) movements essential to the glymphatic flux remain largely unclear. Recent studies have reported that widespread, high-amplitude spontaneous brain activations in the drowsy state and during sleep, which are shown as large global signal peaks in resting-state fMRI, is coupled with the CSF movements, suggesting their potential link to the glymphatic flux and metabolite clearance. By analyzing multimodal data from the Alzheimers Disease Neuroimaging Initiative project, here we showed that the coupling between the global fMRI signal and CSF influx is correlated with AD-related pathology, including various risk factors for AD, the severity of AD-related diseases, the cortical amyloid-{beta} level, and the cognitive decline over a two-year follow-up. These results provide critical initial evidence for involvement of sleep-dependent global brain activity, as well as the associated physiological modulations, in the clearance of AD-related brain waste.

neuroscience↗

bioRxiv2020

Inhibition of Pten activity promotes IB4 positive sensory neuronal axon growth

Traumatic nerve injuries have become a common clinical problem, and axon regeneration is a critical process in the successful functional recovery of the injured nervous system. In this study, we found that peripheral axotomy reduce total PTEN expression in adult sensory neurons, however, it did not alter the expression level of PTEN in IB4-positive sensory neurons. Additionally, our results indicate that the artificial inhibition of PTEN markedly promotes adult sensory axon regeneration, including IB4-positive neuronal axon growth. Thus, our results provide strong evidence that PTEN is a prominent repressor of adult sensory axon regeneration, especially in IB4-positive neurons.

neuroscience↗

bioRxiv2020

Hypercholesterolemia risk associated GPR146 is an orphan G-protein coupled receptor that regulates blood cholesterol level in human and mouse

Genome-wide association studies (GWAS) have identified hundreds of genetic variants associated with dyslipidemia. However, about 95% of of these variants are located in genome noncoding regions and cluster in different loci. The disease-causing variant for each locus and underline mechanism remain largely unknown. We systematically analyzed these noncoding variants and found that rs1997243 is the disease-causing variant in locus 7p22, which is strongly associated with hypercholesterolemia. The rs1997243 risk allele is associated with increased expression of GPR146 in human and targeted activation of the rs1997243 site specifically up regulates GPR146 expression in cultured cells. GPR146 is an orphan G-protein coupled receptor that is located on plasma membrane and responses to stimulation of heat-inactivated serum. Disrupting gpr146 specifically in the liver decreases the blood cholesterol level and prevents high-fat or high-fat high-cholesterol diets induced hypercholesterolemia in mice. Thus we uncovered a novel G-protein coupled receptor that regulates blood cholesterol level in both human and mouse. Our results also suggest that antagonizing GPR146 function will be an effective strategy to treat hypercholesterolemia.

genetics↗

bioRxiv2019

Hsa_circ_0001947 suppresses acute myeloid leukemia progression by sponging hsa-miR-329-5p and regulating CREBRF expression

Acute myeloid leukemia (AML) is a heterogeneous group of diseases resulting from clonal transformation of hematopoietic precursors through the acquisition of chromosomal rearrangements and multiple gene mutations. Accumulating evidence has indicated that aberrantly expressed circular RNAs (circRNAs) are involved in cancer development and progression. However, their clinical values and biological roles in AML remain unclear. In this study, we identified the aberrantly down-regulated profile of hsa_circ_0001947 in AML through microarray analysis and validated it with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Then, we explored the clinical significance, biological functions and regulatory mechanisms of hsa_circ_0001947 in AML patients. The results showed that lower hsa_circ_0001947 expression was positively correlated with higher leukemia cells in bone marrow or peripheral blood, indicating poor prognosis. Further, bioinformatics analysis demonstrated hsa_circ_0001947-hsa-miR-329-5p-CREBRF network. Down-regulation of hsa_circ_0001947 by siRNA promoted cell proliferation, inhibited apoptosis, reduced drug resistance of AML cells, and also decreased the expression of its targeted gene, CREBRF. The mimics of hsa-miR-329-5p reduced drug resistance and decreased the expression of CREBRF, while its inhibitor manifested anti-leukemia effects and increased CREBRF expression. In vivo studies revealed that silencing hsa_circ_0001947 promoted the tumor growth in BALB/c nude mice. Collectively, our findings suggest that hsa_circ_0001947 functions as a tumor inhibitor to suppress AML cell proliferation through hsa-miR-329-5p/CREBRF axis, which would be a novel target for AML therapy.

cancer biology↗

bioRxiv2019

Neuroimaging contrast across the cortical hierarchy is the feature maximally linked to behavior and demographics

We employed a data-driven canonical correlation analysis to investigate the population covariance of whole-brain cortical thickness, resting-state functional connectivity, and hundreds of behavioral/demographic measures in a large cohort of individuals. We found that the maximal thickness-behavior correlation and the maximal connectivity-behavior correlation are largely converged along the same direction across subjects, which is characterized by very specific modulations of all three modalities. Along this direction, individuals tend to have more positive and less negative behavioral/demographic traits, and more importantly, their functional connectivity and cortical thickness show a similar divergent modulation across the cortical hierarchy: thinner cortex and stronger functional connectivity at the higher-order cognitive regions whereas thicker cortex and weaker connectivity at the lower-order sensory/motor areas. These findings provide a unique link between structural and functional brain organizations and human behavior. Specifically, they suggest that the cross-hierarchy contrast of structural and functional brain measures may be a specific feature linked to the overall goodness of behavior and demographics.

neuroscience↗

bioRxiv2018

Transient arousal modulations are responsible for resting-state functional connectivity changes associated with head motion

Correlations of resting-state functional magnetic resonance imaging (rsfMRI) signals are being widely used for assessing functional brain connectivity in health and disease. However, an association was recently observed between rsfMRI connectivity modulations and the head motion parameters and regarded as a causal relationship, which has raised serious concerns about the validity of many rsfMRI findings. Here, we studied the origin of this rsfMRI-motion association and its relationship to arousal modulations. By using a template-matching method to locate arousal-related fMRI changes, we showed that the effects of high motion time points on rsfMRI connectivity are largely due to their significant overlap with arousal-affected time points. The finding suggests that the association between rsfMRI connectivity and the head motion parameters arises from their co-modulations at transient arousal modulations, and this information is critical not only for proper interpretation of motion-associated rsfMRI connectivity changes but also for controlling the potential confounding effects of arousal modulation on rsfMRI metrics.

neuroscience↗

bioRxiv2018

Narcolepsy risk loci are enriched in immune cells and suggest autoimmune modulation of the T cell receptor repertoire

Type 1 narcolepsy (T1N) is a neurological condition, in which the death of hypocretin-producing neurons in the lateral hypothalamus leads to excessive daytime sleepiness and symptoms of abnormal Rapid Eye Movement (REM) sleep. Known triggers for narcolepsy are influenza-A infection and associated immunization during the 2009 H1N1 influenza pandemic. Here, we genotyped all remaining consented narcolepsy cases worldwide and assembled this with the existing genotyped individuals. We used this multi-ethnic sample in genome wide association study (GWAS) to dissect disease mechanisms and interactions with environmental triggers (5,339 cases and 20,518 controls). Overall, we found significant associations with HLA (2 GWA significant subloci) and 11 other loci. Six of these other loci have been previously reported (TRA, TRB, CTSH, IFNAR1, ZNF365 and P2RY11) and five are new (PRF1, CD207, SIRPG, IL27 and ZFAND2A). Strikingly, in vaccination-related cases GWA significant effects were found in HLA, TRA, and in a novel variant near SIRPB1. Furthermore, IFNAR1 associated polymorphisms regulated dendritic cell response to influenza-A infection in vitro (p-value =1.92*10-25). A partitioned heritability analysis indicated specific enrichment of functional elements active in cytotoxic and helper T cells. Furthermore, functional analysis showed the genetic variants in TRA and TRB loci act as remarkable strong chain usage QTLs for TRAJ*24 (p-value = 0.0017), TRAJ*28 (p-value = 1.36*10-10) and TRBV*4-2 (p-value = 3.71*10-117). This was further validated in TCR sequencing of 60 narcolepsy cases and 60 DQB1*06:02 positive controls, where chain usage effects were further accentuated. Together these findings show that the autoimmune component in narcolepsy is defined by antigen presentation, mediated through specific T cell receptor chains, and modulated by influenza-A as a critical trigger.

genetics↗

bioRxiv2017

The pomegranate (Punica granatum L.) genome provides insights into fruit quality and ovule developmental biology

Pomegranate (Punica granatum L.) with an uncertain taxonomic status has an ancient cultivation history, and has become an emerging fruit due to its attractive features such as the bright red appearance and the high abundance of medicinally valuable ellagitannin-based compounds in its peel and aril. However, the absence of genomic resources has restricted further elucidating genetics and evolution of these interesting traits. Here we report a 274-Mb high-quality draft pomegranate genome sequence, which covers approximately 81.5% of the estimated 336 Mb genome, consists of 2,177 scaffolds with an N50 size of 1.7 Mb, and contains 30,903 genes. Phylogenomic analysis supported that pomegranate belongs to the Lythraceae family rather than the monogeneric Punicaceae family, and comparative analyses showed that pomegranate and Eucalyptus grandis shares the paleotetraploidy event. Integrated genomic and transcriptomic analyses provided insights into the molecular mechanisms underlying the biosynthesis of ellagitannin-based compounds, the color formation in both peels and arils during pomegranate fruit development, and the unique ovule development processes that are characteristic of pomegranate. This genome sequence represents the first reference in Lythraceae, providing an important resource to expand our understanding of some unique biological processes and to facilitate both comparative biology studies and crop breeding.

genomics↗

bioRxiv2017

The depletion of MARVELD1 leads to placenta accreta via integrin β4-dependent trophoblast cell invasion

AstractThe mammalian placenta is a remarkable organ. It serves as the interface between the mother and the fetus. Proper invasion of trophoblast cells into the maternal decidua is required for a successful pregnancy. Previous studies have found that the adhesion molecule integrin {beta}4 plays important roles during trophoblast cell invasion. Here, we found that the overall birth rate of the MARVELD1 knockout mouse is much lower than that of the wild-type mouse (P<0.001). In E18.5 MARVELD1 knockout mice, we observed an over-invasion of trophoblast cells, and indeed, the pregnant mice had a partial placenta accreta phenotype. The HTR8/SVneo cell line was used as an in vitro model to elucidate the underlying mechanisms of MARVELD1-mediated trophoblast invasion. We detected a diminished expression of integrin {beta}4 upon the downregulation of MARVELD1 and enhanced migration and invasive abilities of trophoblast cells both in vivo and in vitro. The integrin {beta}4 rescue assay also supported the results. In conclusion, this study found that MARVELD1 mediated the invasion of trophoblast cells via regulating the expression of integrin {beta}4.

developmental biology↗