Qiang Qiu’s research while affiliated with Northwestern Polytechnical University and other places

Lungs are essential respiratory organs in terrestrial vertebrates, present in most bony fishes but absent in cartilaginous fishes, making them an ideal model for studying organ evolution. Here we analysed single-cell RNA sequencing data from adult and developing lungs across vertebrate species, revealing significant similarities in cell composition, developmental trajectories and gene expression patterns. Surprisingly, a large proportion of lung-related genes, coexpression patterns and many lung enhancers are present in cartilaginous fishes despite their lack of lungs, suggesting that a substantial genetic foundation for lung development existed in the last common ancestor of jawed vertebrates. In addition, the 1,040 enhancers that emerged since the last common ancestor of bony fishes probably contain lung-specific elements that led to the development of lungs. We further identified alveolar type 1 cells as a mammal-specific alveolar cell type, along with several mammal-specific genes, including ager and sfta2, that are highly expressed in lungs. Functional validation showed that deletion of sfta2 in mice leads to severe respiratory defects, highlighting its critical role in mammalian lung features. Our study provides comprehensive insights into the evolution of vertebrate lungs, demonstrating how both regulatory network modifications and the emergence of new genes have shaped lung development and specialization across species.

Background Electric eels evolved remarkable electric organs that enable them to instantaneously discharge hundreds of volts for predation, defense, and communication. However, the absence of a high-quality reference genome has extremely constrained the studies of electric eels in various aspects. Results Using high-depth, multiplatform sequencing data, we successfully assembled the first telomere-to-telomere high-quality reference genome of Electrophorus electricus, which has a genome size of 833.43 Mb and comprises 26 chromosomes. Multiple evaluations, including N50 statistics (30.38 Mb), BUSCO scores (97.30%), and mapping ratio of short-insert sequencing data (99.91%), demonstrate the high contiguity and completeness of the electric eel genome assembly we obtained. Genome annotation predicted 396.63 Mb repetitive sequences and 20,992 protein-coding genes. Furthermore, evolutionary analyses indicate that Gymnotiformes, which the electric eel belongs to, has a closer relationship with Characiformes than Siluriformes and diverged from Characiformes 95.00 million years ago. Pairwise sequentially Markovian coalescent analysis found a sharply decreased trend of the population size of E. electricus over the past few hundred thousand years. Furthermore, many regulatory factors related to neurotransmitters and classical signaling pathways during embryonic development were significantly expanded, potentially contributing to the generation of high-voltage electricity. Conclusions This study not only provided the first high-quality telomere-to-telomere reference genome of E. electricus but also greatly enhanced our understanding of electric eels.

Adult mammals are unable to regenerate bulky bone tissues, making large bone defects clinically challenging. Deer antler represents an exception to this rule, exhibiting the fastest bony growth in mammals, offering a unique opportunity to explore novel strategies for rapid bone regeneration. Here, a bone graft exploiting the biochemical, biophysical, and structural characteristics of antlers is constructed. It is decellularized antler cancellous bone (antler‐DCB) to obtain a bone scaffold. Then, an antler‐based bone graft is constructed by integrating antler‐DCB with antler‐derived biological signals, delivered by extracellular vesicles (EVs) from antler blastema progenitor cells (ABPCs), a novel stem cells responsible for antlerogenesis is discovered. The antler‐based bone graft transformed bone marrow stromal cells into cells with an ABPC‐like phenotype and transcriptomic signature. In vivo, the antler‐based graft triggered rapid bone formation in a rat model, with doubled volume of newly formed bones than commercial DCBs. In addition, the antler‐based graft orchestrated a coordinated process of vascularization, neurogenesis, and immunomodulation during osteogenesis, partially imitating early antlerogenesis. These findings provide practical insights to develop a therapeutic intervention for treating severe bone defects.

Crabs encompass the infra-orders Brachyura and Anomura, collectively constitute the clade Meiura within order Decapoda. Despite their considerable diversity, genomic resources for crabs remain scarce, hindering our understanding of their phylogeny and genetic mechanisms underlying such unique traits as carcinization. To address these questions, here we sequenced genomes of 10 crab species covering all currently controversial taxonomies at section level. Our whole-genome phylogenetic results support Raninoida is closer to Eubrachyura rather than Dromiacea, challenging the traditional classifications. Notably, the freshwater crab subsection Potamoida, represented by S. planum, is found to be more closely related to subsection Thoracotremata than to Heterotremata as previously suggested, indicating that crab classification based solely on morphology may be misleading. Our results also clarify that the family Gecarcinidae should be classified into Thoracotremata, contrary to previous placements in Heterotremata. Comparative genomic analyses identified lineage-specific families related to crab traits, including ionotropic glutamate receptors, neurotransmitters, and energy metabolism. Additionally, transcriptomic studies of Chinese mitten crab larval stages suggest that some lineage-specific genes such as ghrA, and TCB2, may account for the prominent carcinization in brachyurans. This study not only significantly expands the genomic repository for crabs, but also provides insights into the phylogeny and trait evolution of crabs.

Antler is the only organ that can fully regenerate annually in mammals. However, the regulatory pattern and mechanism of gene expression and cell differentiation during this process remain largely unknown. Here, we obtain comprehensive assembly and gene annotation of the sika deer ( Cervus nippon ) genome. Together with large-scale chromatin accessibility and gene expression data, we construct gene regulatory networks involved in antler regeneration, identifying four transcription factors, MYC , KLF4 , NFE2L2 , and JDP2 with high regulatory activity across whole regeneration process. Comparative studies and luciferase reporter assay suggest the MYC expression driven by a cervid-specific regulatory element might be important for antler regenerative ability. We further develop a model called cTOP which integrates single-cell data with bulk regulatory networks and find PRDM1 , FOSL1 , BACH1 , and NFATC1 as potential pivotal factors in antler stem cell activation and osteogenic differentiation. Additionally, we uncover interactions within and between cell programs and pathways during the regeneration process. These findings provide insights into the gene and cell regulatory mechanisms of antler regeneration, particularly in stem cell activation and differentiation.

Limbs are a defining characteristic of tetrapods, yet numerous taxa, primarily among amphibians and reptiles, have independently lost limbs as an adaptation to new ecological niches. To elucidate the genetic factors contributing to this convergent limb loss, we present a 12 Gb chromosome-level assembly of the Banna caecilian (Ichthyophis bannanicus), a limbless amphibian. Our comparative analysis, which includes the reconstruction of amphibian karyotype evolution, reveals constrained gene length evolution in a subset of developmental genes across three large genomes. Investigation of limb development genes uncovered the loss of Grem1 in caecilians and Tulp3 in snakes. Interestingly, caecilians and snakes share a significantly larger number of convergent degenerated conserved non-coding elements (dCNEs) than limbless lizards, which have a shorter evolutionary history of limb loss. These convergent dCNEs overlap significantly with active genomic regions during mouse limb development and are conserved in limbed species, suggesting their essential role in limb patterning in the tetrapod common ancestor. While most convergent dCNEs emerged in the jawed vertebrate ancestor, coinciding with the origin of paired appendage, more recent dCNEs also contribute to limb development, as demonstrated through functional experiments. Our study provides novel insights into the regulatory elements associated with limb development and loss, offering an evolutionary perspective on the genetic basis of morphological specialization.

The emergence of highly specific fins, among most fish that own the conventional unpaired (median fins) and two pairs of fins, is regarded as an innovative survival strategy during fish evolution. The spiny red gurnard serves as a representative model for studying the exaptation of fins, which have acquired new functions such as sensory perception. Through genome sequencing and single-cell RNA-seq data, we identified a bony fish-originated olfactory receptor gene homologues expressed in a subset of epithelial cells of spiny red gurnard’s fin ray. Molecular interaction analyses suggested that the interaction between this encoded protein and betaine, formed through two key lysine residues, may occur on the epithelial cell membrane. Behavioral assays further demonstrated more sensitive response in spiny red gurnard to betaine compared to other benthic fish. Our findings highlight the potential role of ancient genes in driving exaptation through site mutations and recruitment to specific regions, providing new insights into the molecular mechanism of fin ray’s sensory adaptations in fish.

The evolution of the vertebrate liver is a prime example of the evolution of complex organs, yet the driving genetic factors behind it remain unknown. Here we study the evolutionary genetics of liver by comparing the amphioxus hepatic caecum and the vertebrate liver, as well as examining the functional transition within vertebrates. Using in vivo and in vitro experiments, single-cell/nucleus RNA-seq data and gene knockout experiments, we confirm that the amphioxus hepatic caecum and vertebrate liver are homologous organs and show that the emergence of ohnologues from two rounds of whole-genome duplications greatly contributed to the functional complexity of the vertebrate liver. Two ohnologues, kdr and flt4, play an important role in the development of liver sinusoidal endothelial cells. In addition, we found that liver-related functions such as coagulation and bile production evolved in a step-by-step manner, with gene duplicates playing a crucial role. We reconstructed the genetic footprint of the transfer of haem detoxification from the liver to the spleen during vertebrate evolution. Together, these findings challenge the previous hypothesis that organ evolution is primarily driven by regulatory elements, underscoring the importance of gene duplicates in the emergence and diversification of a complex organ.

Lungs, essential for terrestrial vertebrates and present in bony fishes but absent in cartilaginous fishes, provide an ideal model for studying organ origination. Our study analyzed single-cell RNA sequencing data from mature and developing vertebrate lungs, revealing substantial similarities in cell composition, developmental trajectories and gene expression pattern across species. Notably, most lung-related genes are also present in cartilaginous fishes, indicating that gene presence alone does not guarantee lung development. We identified thousands of lung regulatory elements specific to bony fishes, with higher concentrations around genes such as tbx4 and the hoxb gene cluster, highlighting the critical role of regulatory changes in lung emergence. These regulatory changes might contribute to unique co-expression patterns in lung epithelial cells, such as those related to pulmonary surfactants and cell morphology. Our research also revealed that AT1 cells are specific to mammals, and we identified a mammal-specific gene, sfta2. Knockout experiments demonstrated that sfta2 deletion causes severe respiratory defects in mice, underscoring its critical role in specialized mammalian lungs. In conclusion, our results demonstrate that the origin and evolution of lungs are driven by a complex interplay of regulatory network modifications and the emergence of new genes, underscoring the multifaceted nature of organ evolution.