Biology subjects

Si, S.

Publications and source records attributed to Si, S..

7 recordsLinked to original sources

bioRxiv2026

cellNexus: Quality control, annotation, aggregation and analytical layers for the Human Cell Atlas data

Large-scale single-cell atlases such as the Human Cell Atlas have transformed our understanding of human biology. Yet, the lack of a robust framework that standardises quality control, expands cellular annotation, and adds normalisation and analytical layers, limits multi-study analyses and the usefulness of this resource. Here we present cellNexus, a comprehensive resource that enhances the Human Cell Atlas collection into analysis-ready data by linking quality control layers, metadata enrichment, expression normalisation, analysis and data aggregation. These enhancements enable robust large-scale statistical modelling across studies, exemplified here by a multi-tissue map of immune cell communication during ageing. All harmonised layers are accessible via a public web interface and with R and Python APIs. By providing continuous integration with CELLxGENE releases, cellNexus transforms large cell atlas corpora into an accessible, reproducible, interoperable foundation for large-scale biological discovery and the next generation of single-cell foundation models.

bioinformatics↗

bioRxiv2025

Functional Mapping and Engineering of the Sec Translocon Unlocked by a Cell-Free System

Almost all proteins are inserted or translocated across membranes by the universally conserved Sec translocon. Despite its central role, experimental access to Sec function has remained limited. Here, we present a cell-free protein synthesis platform that inserts SecYEG into synthetic vesicles, enabling direct testing of Sec in real-time and high-throughput, circumventing longstanding viability constraints. Screening 300 Sec variants in a single experiment, we consolidate three decades of Sec research, while vastly expanding mutant diversity for structure-function insights. Mapping over 30 functionally critical regions that modulate Sec activity across three orders of magnitude, we uncover dozens of super-active variants. We further leverage our system to increase membrane protein quality and nanobody export, highlighting the potential of our system for advancing applications in synthetic biology and biotechnology.

molecular biology↗

bioRxiv2025

Structural basis of neurofibromin tetramerization and dimer-tetramer equilibrium

Human neurofibromin (NF1) is a tumor suppressor multidomain protein known to regulate cellular functions as a dimer. Using cryo-EM, we discovered that neurofibromin can form more highly organized structures and describe tetramerization and a dynamic dimer-to-tetramer equilibrium with extensive interlocked interfaces as well as structural flexibility. The new tetramer structure generates and modifies interaction surfaces and controls protein functions such as microtubule recruitment, thereby providing novel insights into cellular functions.

molecular biology↗

bioRxiv2024

Rapid evolution of fine-scale recombination during domestication

Recombination serves as a pivotal force propelling the evolution of genomic diversity in sexually reproducing organisms. Despite its fundamental role, the evolutionary dynamics of recombination rates and their implications for genome evolution remain largely elusive. The domestication of animals, which is characterized by dynamic selection pressures, offers a unique lens to explore this issue. Here, we constructed a fine-scale recombination map leveraging whole-genome data from domestic chickens, encompassing both contemporary commercial breeds and the wild progenitor, the Red Junglefowl (RJF). Our analysis revealed the rapid evolution of the recombination landscape within and across chicken populations, with significant variation in recombination coldspots and hotspots, particularly in commercial breeds. The occurrence of coldspots and the disappearance of hotspots are closely associated with selective sweeps.Contrary to prevailing observations in most species, we observed a weakly negative correlation between recombination rates and the frequency of introgressed ancestry from other RJF subspecies. Our findings provide valuable insights into the intricate interplay of evolutionary forces shaping the evolution of recombination.

evolutionary biology↗

bioRxiv2024

Epigenetic delineation of the earliest cardiac lineage segregation by single-cell multi-omics

The mammalian heart is formed from multiple mesoderm-derived cell lineages. However, it remains largely unknown when and how the specification of mesoderm towards cardiac lineages is determined. Here, we systematically depict the transcriptional trajectories toward cardiomyocyte in early mouse embryo, and characterize the epigenetic landscapes underlying the early mesodermal lineage specification by single-cell multi-omics analyses. The analyses also reveal distinct core regulatory networks (CRN) in controlling specification of mesodermal lineages. We further demonstrate the essential role HAND1 and FOXF1 in driving the earliest cardiac progenitors specification. These key transcription factors occupy at distinct enhancers, but function synergistically and hierarchically to regulate the expression of cardiac-specific genes. In addition, HAND1 is required for exiting from the nascent mesoderm program, while FOXF1 is essential for driving cardiac differentiation during juxta-cardiac field (JCF) specification. Our findings establish transcriptional and epigenetic determinants specifying the early cardiac lineage, providing insights for the investigation of congenital heart defects.

molecular biology↗

bioRxiv2020

The Genetics and Evolution of Eye Color in Domestic Pigeons (Columba livia)

The avian eye color, generally referred to the color of the iris, results from both pigments and structural coloration. Avian iris colors exhibit striking interspecific and, in some domestic species, intraspecific variations, suggesting unique evolutionary and ecological histories. Here we tackled the genetic basis of the pearl (white) iris color in domestic pigeons (Columba livia), to elucidate the largely unknown genetic mechanism underlying the evolution of avian iris coloration. Using a genome-wide association study (GWAS) in 92 pigeons, we mapped the pearl iris trait to a 9 kb region and a facilitative glucose transporter gene SLC2A11B. A nonsense mutation W49X leading to a premature stop codon in SLC2A11B was identified as the causal variant. Transcriptome analysis suggested that SLC2A11B loss-of-function may downregulate the xanthophore-differentiation gene CSF1R, and a key gene GCH1 involved in biosynthesis of pteridine, whose absence results in pearl iris. Coalescence and phylogenetic analyses indicated the mutation originated about 5,400 years ago coinciding with the onset of pigeon domestication, while positive selection was detected likely associated with artificial breeding. Within Aves, potentially impaired SLC2A11B was found in 10 species from six distinct lineages correlated to their signature brown or blue eyes. Analysis of vertebrate SLC2A11B orthologs revealed relaxed selection in the avian clade, consistent with the scenario that, during and after avian divergence from reptile ancestor, the SLC2A11B-involved development of dermal chromatophores likely degenerated due to feather coverage. Our findings provide new insight into the mechanism of avian iris color variations and the evolution of pigmentation in vertebrates.

genetics↗

bioRxiv2019

Paternal Indifference and neglect in early life and Creativity: Exploring the Moderating Role of TPH1 genotype and Offspring’s Gender

For further understanding the joint contribution of environment, heredity and gender to creativity, the present research examined the prospective impact of paternal indifference & neglect in early life, TPH1 rs623580, offsprings gender, and the interaction effects thereof on creativity in five hundred and thirty-nine unrelated healthy Chinese undergraduate students. Paternal indifference & neglect in early life was assessed on the Parental Bonding Instrument (PBI) and creativity on the Runco Creativity Assessment Battery (rCAB). Results showed significant paternal indifference & neglect x TPH1 genotype and TPH1 genotype x offsprings gender interaction effects when predicting creativity. Specifically, paternal indifference & neglect in early life negatively predicted creativity in youth when individuals carry A allele of TPH1 (rs623580). In addition, male individuals who carry A allele were linked with lower level of flexibility compared to TT homozygote individuals. No significant three-way interaction was found. Findings from the current study suggested that the A allele of TPH1 (rs623580) might be a risk allele for creativity, and the long-term negative influence of paternal indifference & neglect in early life on individuals creativity in youth depending on TPH1 genotype.

genetics↗