Biomedical subjects

Jiandong Liu

Publications and source records attributed to Jiandong Liu.

10 recordsLinked to original sources

PubMed2026

Spatially guided in vivo single-cell functional genomics of postnatal heart.

Understanding how spatial organization and cell-cell interactions shape gene regulatory programs is central to decoding tissue development and function. The transition at birth, marked by increased circulatory demands and rapid tissue growth, requires precise spatiotemporal coordination of cardiac maturation. In this study, we generated a high-resolution spatial and temporal atlas of the postnatal mouse heart by integrating single-nucleus RNA sequencing with image-based spatial transcriptomics. This framework revealed dynamic cellular interactions, niche-specific signaling and transcriptional programs guiding cardiomyocyte maturation. To functionally test prioritized regulators in vivo and at scale, we developed PIP-seq (probe-based indel-detectable Perturb-seq), a high-throughput platform that detects single guide RNA identity, infers gene editing and profiles transcription from fixed nuclei. Applying PIP-seq to the developing postnatal heart, we identified 21 previously uncharacterized regulators of cardiomyocyte maturation, including genes essential for sarcomere assembly, metabolic reprogramming and electrophysiological transitions. Together, our findings define how microenvironmental signals and intrinsic gene programs cooperate to guide heart maturation and establish a broadly applicable framework for functional genomics in complex tissues.

Animals↗

PubMed2025

Charting Postnatal Heart Development Using In Vivo Single-Cell Functional Genomics.

The transition at birth, marked by increased circulatory demands and rapid growth, necessitates extensive remodeling of the heart's structure, function, and metabolism. This transformation requires precise spatial and temporal coordination among diverse cardiac cell types; central to this process is cardiomyocyte maturation, yet the regulatory mechanisms driving these changes remain poorly understood. Here, we present a temporal and spatial atlas of postnatal hearts by integrating single-nucleus transcriptomics with image-based spatial transcriptomics, which uncovers the dynamic regulatory networks of cardiomyocyte maturation. To functionally interrogate candidate regulators in vivo , we developed Probe-based Indel-detectable Perturb-seq (PIP-seq), a high-throughput platform that uses probe-based chemistry to directly capture sgRNA expression, perturbation status, and transcriptomic profiles at single-nucleus resolution. Applying PIP-seq to postnatal cardiac development identified 21 novel regulators of cardiomyocyte maturation, highlighting critical nodal points in this process. Our study establishes a high-resolution framework for dissecting postnatal heart development, underscoring the integrative and highly ordered roles of microenvironment and intercellular communication in cardiomyocyte maturation. Importantly, PIP-seq enables systematic, high-throughput exploration of gene function and networks underlying complex biological processes in their native in vivo context.

Journal Article↗

PubMed2006

Renaturation and purification of ApxII toxin of Actinobacillus pleuropneumoniae.

ApxII toxin is the only Apx toxin that is produced by Actinobacillus pleuropneumoniae serotype 7. In order to determine whether the recombinant ApxII that derived from Escherichia coli (E. coli) expression is faithful to the natural ApxII so that can be used as additional component in vaccine preparation, the structure gene apxIIA of ApxII toxin was expressed in E. coli with prokaryotic expression vector pGEX-6p-1 (formed pGEX-6p-A). pGZRS-C which is A. pleuropneumoniae-E. coli shuttle vector pGZRS-38 expressing the post-transcriptional activation gene apxII C was co-expressed with pGEX-6p-A. The expression product of rApxII A formed inclusion. The inclusion protein was oxidized, refolded and restored hemolytic activity after denaturation, renaturation and purification. The result indicated that E. coli expressed recombinant ApxII toxin has good fidelity, which makes it possible to produce this valuable antigen for vaccine preparation or diagnosis.

Actinobacillus pleuropneumoniae↗

PubMed2006

Antioxidants protect PINK1-dependent dopaminergic neurons in Drosophila.

Parkinson's disease (PD) is the most frequent neurodegenerative movement disorder. Mutations in the PINK1 gene are linked to the autosomal recessive early onset familial form of PD. The physiological function of PINK1 and pathological abnormality of PD-associated PINK1 mutants are largely unknown. We here show that inactivation of Drosophila PINK1 (dPINK1) using RNAi results in progressive loss of dopaminergic neurons and in ommatidial degeneration of the compound eye, which is rescued by expression of human PINK1 (hPINK1). Expression of human SOD1 suppresses neurodegeneration induced by dPINK1 inactivation. Moreover, treatment of dPINK1 RNAi flies with the antioxidants SOD and vitamin E significantly inhibits ommatidial degeneration. Thus, dPINK1 plays an essential role in maintaining neuronal survival by preventing neurons from undergoing oxidative stress, thereby suggesting a potential mechanism by which a reduction in PINK1 function leads to PD-associated neurodegeneration.

Animals↗

PubMed2006

Hedgehog and RAS pathways cooperate in the anterior-posterior specification and positioning of cardiac progenitor cells.

The Drosophila heart is a highly ordered structure with only a limited number of cell types, which are arranged in a stereotyped metameric pattern. Ras signaling has previously been implicated in contributing to heart formation, but how positional information is integrated with this pathway to specify, distinguish and precisely position individual cardiac progenitors within the presumptive heart-forming region are not known. Here, we present evidence that the striped pattern of the secreted factor Hedgehog (Hh), in combination with the RAS pathway, specifies and positions neighboring groups of cardiac progenitors within each segment: the anterior ladybird (lbe)- and the posterior even skipped (eve)-expressing cardiac progenitors. Loss of hh function (while maintaining wg activity) results in the absence of the Eve cells, whereas the Lbe cells are expanded within the cardiac mesoderm. Overexpressing the repressor form of Cubitus interruptus (Ci), a Hh pathway antagonist, also results in expansion of Lbe at the expense of Eve, as does lowering Ras signaling. Conversely, overexpression of Hh or increasing Ras signaling eliminates Lbe expression while expanding Eve within the cardiogenic mesoderm. Increasing Ras signaling in the absence of Hh suggests that the Ras pathway is in part epistatic to Hh. Hh controls dorsal mesodermal Ras signaling by transcriptional regulation of the EGF receptor ligand protease, encoded by rhomboid (rho). Conversely, Hh overexpression can fully inhibit Lbe even when Ras signaling is much reduced, suggesting that Hh also acts in parallel to Ras. We propose that the Eve precursors next to the Hh stripe are distinguished from more distant Lbe precursors by locally augmenting Ras signaling via elevating rho transcripts. Thus, the spatial precision of cell type specification within an organ depends on multiple phases of inductive interaction between the ectoderm and the mesoderm.

Animals↗

PubMed2005

Slit and Robo control cardiac cell polarity and morphogenesis.

Basic aspects of heart morphogenesis involving migration, cell polarization, tissue alignment, and lumen formation may be conserved between Drosophila and humans, but little is known about the mechanisms that orchestrate the assembly of the heart tube in either organism. The extracellular-matrix molecule Slit and its Robo-family receptors are conserved regulators of axonal guidance. Here, we report a novel role of the Drosophila slit, robo, and robo2 genes in heart morphogenesis. Slit and Robo proteins specifically accumulate at the dorsal midline between the bilateral myocardial progenitors forming a linear tube. Manipulation of Slit localization or its overexpression causes disruption in heart tube alignment and assembly, and slit-deficient hearts show disruptions in cell-polarity marker localization within the myocardium. Similar phenotypes are observed when Robo and Robo2 are manipulated. Rescue experiments suggest that Slit is secreted from the myocardial progenitors and that Robo and Robo2 act in myocardial and pericardial cells, respectively. Genetic interactions suggest a cardiac morphogenesis network involving Slit/Robo, cell-polarity proteins, and other membrane-associated proteins. We conclude that Slit and Robo proteins contribute significantly to Drosophila heart morphogenesis by guiding heart cell alignment and adhesion and/or by inhibiting cell mixing between the bilateral compartments of heart cell progenitors and ensuring proper polarity of the myocardial epithelium.

Animals↗

PubMed2005

Embryonic even skipped-dependent muscle and heart cell fates are required for normal adult activity, heart function, and lifespan.

The Drosophila pair-rule gene even skipped (eve) is required for embryonic segmentation and later in specific cell lineages in both the nervous system and the mesoderm. We previously generated eve mesoderm-specific mutants by combining an eve null mutant with a rescuing transgene that includes the entire locus, but with the mesodermal enhancer removed. This allowed us to analyze in detail the defects that result from a precisely targeted elimination of mesodermal eve expression in the context of an otherwise normal embryo. Absence of mesodermal eve causes a highly selective loss of the entire eve-expressing lineage in this germ layer, including those progeny that do not continue to express eve, suggesting that mesodermal eve precursor specification is not implemented. Despite the resulting absence of a subset of muscles and pericardial cells, mesoderm-specific eve mutants survive to fertile adulthood, providing an opportunity to examine the effects of these developmental abnormalities on adult fitness and heart function. We find that in these mutants, flying ability, myocardial performance under normal and stressed conditions, and lifespan are severely reduced. These data imply a nonautonomous role of the affected pericardial cells and body wall muscles in developing and/or maintaining cardiac performance and possibly other functions contributing to normal lifespan. Given the similarities of molecular-genetic control between Drosophila and vertebrates, these findings suggest that peri/epicardial influences may well be important for proper myocardial function.

Aging↗

PubMed2005

Neuromancer Tbx20-related genes (H15/midline) promote cell fate specification and morphogenesis of the Drosophila heart.

The Tbx family of transcription factors are prominently expressed in the early cardiac primordium throughout the animal kingdom. Mutations in Tbx genes result invariably in defective formation and function of the heart, including congenital heart disease in humans. Similar to their vertebrate counterpart, the Drosophila Tbx20 gene pair, neuromancer1 (nmr1, FlyBase:H15) and neuromancer2 (nmr2, Flybase:mid), exhibits a dynamic expression pattern, including in all contractile myocardial cells. Deletion mutants of nmr1 combined with mesoderm-specific knock-down of nmr2 exhibit phenotypes that suggest nmr is critical for correct specification of the cardiac progenitor populations as well as for morphogenesis and assembly of the contractile heart tube. Loss-of-nmr-function causes a switch in cell fates in the cardiogenic region, in that the progenitors expressing the homeobox gene even skipped (eve) are expanded accompanied by a corresponding reduction of the progenitors expressing the homeobox gene ladybird (lbe). As a result, the number of differentiating myocardial cells is severely reduced whereas pericardial cell populations are expanded. Conversely, pan-mesodermal expression of nmr represses eve, while causing an expansion of cardiac lbe expression, as well as ectopic mesodermal expression of the homeobox gene tinman. In addition, nmr mutants with less severe penetrance exhibit cell alignment defects of the myocardium at the dorsal midline, suggesting nmr is also required for cell polarity acquisition of the heart tube. In exploring the regulation of nmr, we find that the GATA factor Pannier is essential for cardiac expression, and acts synergistically with Tinman in promoting nmr expression. Moreover, reducing nmr function in the absence of pannier further aggravates the deficit in cardiac mesoderm specification. Taken together, the data suggest that nmr acts both in concert with and subsequent to pannier and tinman in cardiac specification and differentiation. We propose that nmr is another determinant of cardiogenesis, along with tinman and pannier.

Animals↗

PubMed2002

Simulation of rice biomass accumulation by an extended logistic model including influence of meteorological factors.

The biomass (X) of a biological population, described by growth models, depends only on time (t), i.e., X = f(t). Some parameters in these models are frequently taken as constants, but they may vary with growth processes under different ecological conditions. An extended logistic model including changes in the influence of meteorological factors is developed to simulate biomass accumulation processes of rice sown on different dates. The model may be generally described as X = f (p, t), in which p stands for meteorological factors. The model can be used to generalize population growth processes in experiments carried out under different environments. It is shown that the model may account for 96.6% of the variance of rice biomass on the basis of sowing dates, developmental stage, solar radiation and temperature in the Yangtze River valley in China.

Biomass↗

PubMed2002

[Simulation of N2O emissions in agroecosystems].

A numerical model for simulating N2O emissions in agroecosystem was established. Validation of the model with the observed data showed that the model simulated the process of N2O emissions in fields fairly well. The numerical analysis showed that the N2O emissions were interrelated well with average temperature during rice growth periods. Analysis of N2O emissions and meteorological factors by using power spectrum found that the change of N2O emissions had 7-9 year cycles. Sensitivity test showed that the N2O emission increased with temperature enhancement.

Air Pollution↗