Biology subjects

Zhou, J.

Publications and source records attributed to Zhou, J..

At least 397 records · Page 22Linked to original sources

bioRxiv2022

PTH regulates osteogenesis and suppresses adipogenesis through Zfp 467 in a feed-forward, cyclic AMP-dependent manner

Conditional deletion of the PTH1R in mesenchymal progenitors reduces osteoblast differentiation, enhances marrow adipogenesis and increases zinc finger protein 467 (Zfp467) expression. In contrast, genetic loss of Zfp467 increased Pth1r expression and shifts mesenchymal progenitor cell fate towards osteogenesis and higher bone mass. In this study we hypothesized that PTH1R and ZFP467 could constitute a feedback loop that facilitates PTH-induced osteogenesis and that conditional deletion of Zfp467 in osteogenic precursors would lead to high bone mass. We report that PrrxCre Zfp467 but not AdipoCre Zfp467 mice exhibit an identical phenotype to the Zfp467-/-mice with high bone mass and greater osteogenic differentiation We also found that PTH suppressed Zfp467 expression primarily via the cyclic AMP/PKA pathway. Not surprisingly, PKA activation inhibited the expression of Zfp467 and gene silencing of Pth1r caused an increase in Zfp467 mRNA transcription. Dual fluorescence reporter assays and confocal immunofluorescence demonstrated that genetic deletion of Zfp467 resulted in higher nuclear translocation of p50 that binds to the P2 promoter of the Pth1r and increased its transcription. As expected, Zfp467-/- cells had enhanced production of cyclic AMP and increased glycolysis in response to exogenous PTH. Additionally, the osteogenic response to PTH was also enhanced in Zfp467 -/-calvarial osteoblasts, and the pro-osteogenic effect of Zfp467 deletion was blocked by gene silencing of Pth1r or a PKA inhibitor. In conclusion, our findings suggest that loss or PTH1R-mediated repression of Zfp467 results in a pathway that increases Pth1r transcription via p50 and thus cellular responsiveness to PTH, ultimately leading to enhanced bone formation.

cell biology↗

bioRxiv2022

Epigenomic and chromosomal architectural reconfiguration in developing human frontal cortex and hippocampus

The human frontal cortex and hippocampus play critical roles in learning and cognition. We investigated the epigenomic and 3D chromatin conformational reorganization during the development of the frontal cortex and hippocampus, using more than 53,000 joint single-nucleus profiles of chromatin conformation and DNA methylation (sn-m3C-seq). The remodeling of DNA methylation predominantly occurs during late-gestational to early-infant development and is temporally separated from chromatin conformation dynamics. Neurons have a unique Domain-Dominant chromatin conformation that is different from the Compartment-Dominant conformation of glial cells and non-brain tissues. We reconstructed the regulatory programs of cell-type differentiation and found putatively causal common variants for schizophrenia strongly overlap with chromatin loop-connected, cell-type-specific regulatory regions. Our data demonstrate that single-cell 3D-regulome is an effective approach for dissecting neuropsychiatric risk loci.

genomics↗

bioRxiv2022

MeCP2 regulates Gdf11, a dosage-sensitive gene critical for neurological function

Loss- and gain-of-function of MeCP2 causes Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), respectively. MeCP2 binds methyl-cytosines to finely tune gene expression in the brain, though identifying genes robustly regulated by MeCP2 has been difficult. By integrating multiple transcriptomics datasets, we identified that MeCP2 finely regulates Growth differentiation factor 11 (Gdf11). Gdf11 is down-regulated in RTT mouse models and is inversely up-regulated in MDS mouse models. Strikingly, genetically normalizing Gdf11 dosage levels improved several behavioral deficits in a mouse model of MDS. Next, we discovered that losing one copy of Gdf11 alone was sufficient to cause multiple neurobehavioral deficits in mice, most notably hyperactivity and decreased learning and memory. This decrease in learning and memory was not due to changes in proliferation or numbers of progenitor cells in the hippocampus. Lastly, loss of one copy of Gdf11 decreased longevity and survival in mice, corroborating its putative role in aging. Our data demonstrate that Gdf11 dosage is important for brain function.

neuroscience↗

bioRxiv2022

Deep Learning model accurately classifies metastatic tumors from primary tumors based on mutational signatures

Metastatic propagation is the leading cause of death for most cancers. Prediction and elucidation of metastatic process is crucial for the therapeutic treatment of cancers. Even though somatic mutations have been directly linked to tumorigenesis and metastasis, it is less explored whether the metastatic events can be identified through genomic mutation signatures, a concise representation of the mutational processes. Here, applying mutation signatures as input features calculated from Whole-Exome Sequencing (WES) data of TCGA and other metastatic cohorts, we developed MetaWise, a Deep Neural Network (DNN) model. This model accurately classified metastatic tumors from primary tumors. Signatures of non-coding mutations also have a major impact on the model performance. SHapley Additive exPlanations (SHAP) and Local Surrogate (LIME) analysis into the MetaWise model identified several mutational signatures directly correlated to metastatic spread in cancers, including APOBEC-mutagenesis, UV-induced signatures and DNA damage response deficiency signatures.

cancer biology↗

bioRxiv2022

Transient, developmental exposure to patient-derived anti-NMDA receptor autoantibodies causes long-term axonal and behavioral defects

NMDA receptor mediated autoimmune encephalitis (NMDAR-AE) frequently results in persistent sensory-motor deficits, especially in children, yet the underlying mechanisms remain unclear. This study investigated the long-term effects of exposure to a patient-derived GluN1-specific monoclonal antibody (mAb) during a critical developmental period (from postnatal day 3 to day 12) in mice. We observed long-lasting sensory-motor deficits characteristic of NMDAR-AE, along with permanent changes in callosal axons within the primary somatosensory cortex (S1) in adulthood, including increased terminal branch complexity. This complexity was associated with paroxysmal recruitment of neurons in S1 in response to callosal stimulation. Particularly during complex motor tasks, mAb3-treated mice exhibited significantly reduced inter-hemispheric functional connectivity between S1 regions, consistent with pronounced sensory-motor behavioral deficits. These findings suggest that transient exposure to anti-GluN1 mAb during a critical developmental window may lead to irreversible morphological and functional changes in callosal axons, which could significantly impair sensory-motor integration and contribute to long-lasting sensory-motor deficits. Our study establishes a new model of NMDAR-AE and identifies novel cellular and network-level mechanisms underlying persistent sensory-motor deficits in this context. These insights lay the foundation for future research into molecular mechanisms and the development of targeted therapeutic interventions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/510196v3_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@37f452org.highwire.dtl.DTLVardef@1894e46org.highwire.dtl.DTLVardef@171f954org.highwire.dtl.DTLVardef@1a81742_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

PF-D-Trimer, a broadly protective SARS-CoV-2 subunit vaccine: immunogenicity and application

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and still has a considerable impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, the primary responsible for the host immune response upon infection. Here we show the preclinical studies of a broad protective SARS-CoV-2 subunit vaccine developed from our Trimer Domain platform using the Delta spike protein, from antigen design to purification, vaccine evaluation and manufacturability. The prefusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. The immunogenicity studies demonstrated that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous virus challenge. The neutralizing antibodies induced by this vaccine display a cross-reactive capacity against the ancestral WA1 and Delta variants as well as different Omicron, including BA.5.2. The Trimer Domain platform was proven to be a key technology in the rapid production of the PF-D-Trimer vaccine and may be crucial to accelerate the development of updated versions of SARS-CoV-2 vaccines.

immunology↗

bioRxiv2022

Neuronal pentraxin Nptx2 regulates complement activity in the brain

Complement overactivation mediates microglial synapse elimination in neurological diseases like Alzheimers disease and frontotemporal dementia (FTD), but how complement activity is regulated in the brain remains largely unknown. We identified that the secreted neuronal pentraxin Nptx2 binds complement C1q and thereby regulates its activity in the brain. Nptx2-deficient mice show increased complement activity and C1q-dependent microglial synapse engulfment and loss of excitatory synapses. In a neuroinflammation culture model and in aged TauP301S mice, AAV-mediated neuronal overexpression of Nptx2 was sufficient to restrain complement activity and ameliorate microglia-mediated synapse loss. Analysis of human CSF samples from a genetic FTD cohort revealed significantly reduced levels of Nptx2 and Nptx2-C1q protein complexes in symptomatic patients, which correlated with elevated C1q and activated C3. Together, these results show that Nptx2 regulates complement activity and microglial synapse elimination in the healthy and diseased brain and that diminished Nptx2 levels might exacerbate complement-mediated neurodegeneration in FTD patients.

neuroscience↗

bioRxiv2022

The potent broadly neutralizing antibody VIR-3434 controls Hepatitis B and D Virus infection and reduces HBsAg in humanized mice

Background & AimsChronic hepatitis B is a major global public health problem, and coinfection with hepatitis delta virus (HDV) worsens disease outcome. Here, we describe a hepatitis B virus (HBV) surface antigen (HBsAg)-targeting monoclonal antibody (mAb) with the potential to promote functional cure of chronic hepatitis B and D to address this unmet medical need. MethodsHBsAg-specific mAbs were isolated from memory B cells of HBV vaccinated individuals. In vitro neutralization was determined against HBV and HDV enveloped with HBsAg representing eight HBV genotypes. Human liver-chimeric mice were treated twice weekly with a candidate mAb starting three weeks post HBV inoculation (spreading phase) or during stable HBV or HBV/HDV coinfection (chronic phase). ResultsFrom a panel of human anti-HBs mAbs, VIR-3434 was selected and engineered for pre-clinical development. VIR-3434 targets a putative conserved, conformational epitope within the antigenic loop of HBsAg and neutralized HBV and HDV infection with >12,000-fold higher potency than Hepatitis B Immunoglobulins in vitro. Neutralization was pan-genotypic against strains representative of HBV genotypes A-H. In the spreading phase of HBV infection in human liver-chimeric mice, a parental mAb of VIR-3434 (HBC34) prevented HBV dissemination and intrahepatic HBV RNA and cccDNA increase. In the chronic phase of HBV infection or co-infection with HDV, HBC34 treatment decreased circulating HBsAg by >1 log and HDV RNA by >2 logs. ConclusionsThis in vitro and in vivo characterization identified the potent anti-HBs mAb VIR-3434, which reduces circulating HBsAg and HBV/HDV viremia in human liver-chimeric mice. VIR-3434 is currently in clinical development for treatment of patients with chronic hepatitis B or D. Lay summaryChronic infection with hepatitis B virus places approximately 290 million individuals worldwide at risk for severe liver disease and cancer. Currently available treatments result in low rates of functional cure or require lifelong therapy that does not eliminate the risk of liver disease. We isolated and characterized a potent, human antibody that neutralizes hepatitis B and D viruses and reduces infection in a mouse model. This antibody could provide a new treatment for patients with chronic hepatitis B and D. HighlightsO_LIIdentification of a human mAb VIR-3434 that potently neutralizes HBV and HDV C_LIO_LIVIR-3434 targets a conserved, conformational epitope of the HBsAg antigenic loop C_LIO_LIVIR-3434 treatment blocks intrahepatic HBV spread in human liver-chimeric mice C_LIO_LIVIR-3434 treatment reduces circulating HBsAg and HDV RNA in co-infected mice C_LIO_LIData have enabled clinical development of VIR-3434 against chronic hepatitis B/D C_LI

microbiology↗

bioRxiv2022

Metaplasticity: Dark exposure boosts excitability and visual plasticity in adult human cortex

AO_SCPLOWBSTRACTC_SCPLOWAn interlude of dark exposure for about one week is known to shift the excitatory/inhibitory (E/I) balance of the mammalian visual cortex, promoting cortical plasticity across species and accelerating visual recovery in animals that have experienced cortical lesions during development. However, the translational impact of our understanding of dark exposure from animal studies on humans remains elusive. Here, we use magnetic resonance spectroscopy as a probe for E/I balance in the primary visual cortex (V1) to determine the effect of 60-min dark exposure, and measure binocular combination as a behavioral assay to assess visual plasticity in 18 normally sighted human adults (13 females). To induce neuroplastic changes in the observers, 60-min monocular deprivation was performed, which is known to shift sensory eye balance in favor of the previously deprived eye. We report that prior dark exposure strengthens cortical excitability in V1 and boosts visually plasticity in normal adults. Our findings are surprising, given the fact that the interlude is very brief. We present direct evidence that an environmental manipulation that reduces intracortical inhibition can act as a metaplastic facilitator for visual plasticity in adult humans.

neuroscience↗

bioRxiv2022

Life-course social disparities in body mass index trajectories across adulthood: cohort study evidence from China Health and Nutrition Survey

BackgroundThe social disparities in obesity may originate in early life and adult social class. There are various developmental trajectories of overweight/obesity in adulthood. It is unclear how the intergenerational mobility of socioeconomic status influences adult overweight/obesity in China. MethodsWe used longitudinal data from ten waves of the China Health and Nutrition Survey (CHNS) between 1989 and 2015 for our analysis. The group-based trajectory modeling was used to identify BMI trajectories in adulthood. Multinomial logistic regression was adopted to assess the associations between SES and adult BMI trajectories. ResultsAmong a total of 3,138 participants, three latent clusters, including normal-stable BMI (51.4%), progressive overweight group (39.8%), and progressive obesity group (8.8%), were identified. High fathers occupational position, high participants occupation position and educational attainment, respectively, were associated with greater obesity risk. Compared to a stable low life course SES trajectory, a stable high life course SES trajectory was associated with a 2.35-fold risk of obesity, and upward and downward social mobility trajectories increased the risk for overweight/obesity. Individuals in the highest relative to the lowest life course cumulative socioeconomic score group had around twice risk of obesity. ConclusionsThe results emphasize the role of the high SES in early life and life-course SES accumulation, in the obesity intervention in China. FundingAll the work was supported by the National Natural Science Foundation of China (Grant Nos. 72174167, 81602928) and Natural Science Foundation of Shaanxi (2021JM-031).

scientific communication and education↗

bioRxiv2022

DUnet: A deep learning guided protein-ligand binding pocket prediction

Investigating protein-ligand binding sites is the key step in engineering protein/enzyme activity and selectivity. In this study, we developed a 3D convolutional neural network DUnet that derived from DenseNet and UNet for predicting the protein-ligand binding sites. To train DUnet, the features of protein 3D structure were extracted by describing the atomic physical characters, and the ligand binding sites were used as training labels. DUnet was trained using three dataset, the scPDB dataset (collecting of protein-ligand complexes from Protein Data Bank), scPDB and SC6K (collecting of protein-ligand complexes deposited after January 1st, 2018 from Protein Data Bank) datasets, and scPDB and its derived dataset by rotating the samples in the dataset. DUnet displayed better performance than the current state-of-art methods during the benchmark test using independent validation sets, and enlarging the training set contributed to better accuracy. We developed a small dataset contains commonly used industrial enzymes for testing DUnet and found that it was also accurate in predicting the substrate binding sites. We experimentally characterized the substrate binding sites of microbial transglutaminase according to the prediction and showed the significance of these sites. Finally, DUnet was used to predict the ligand binding sites of Swiss-Prot annotated proteins.

bioinformatics↗

bioRxiv2022

Clonal evolution during metastatic spread in high-risk neuroblastoma

High-risk neuroblastoma is generally metastatic and often lethal. Using genomic profiling of 470 sequential and spatially separated samples from 283 patients, we characterize subtype-specific genetic evolutionary trajectories from diagnosis, through progression and end-stage metastatic disease. Clonal tracing timed disease initiation to embryogenesis. Continuous acquisition of structural variants at disease defining loci (MYCN, TERT, MDM2-CDK4) followed by convergent evolution of mutations targeting shared pathways emerged as the predominant feature of progression. At diagnosis metastatic clones were already established at distant sites where they could stay dormant, only to cause relapses years later and spread via metastasis-to-metastasis and polyclonal seeding after therapy.

genomics↗

bioRxiv2022

Macrophage migrates on alternate non-adhesive surfaces

Macrophages migrate across tissues upon immune demand, but their motility on heterogeneous substrates remains unclear. Protein-repelling reagents, e.g., poly(ethylene) glycol (PEG), are routinely employed to resist cell adhering and migrating. Contrary to this perception, we discovered a unique locomotion of macrophages in vitro that they overcome non-adhesive PEG gaps to reach adhesive regions in a mesenchymal mode. Adhesion to adhesive regions was a prerequisite for macrophages to perform further locomotion on the PEG regions, or else they kept a suspended round shape. Podosomes were found highly enriched on the PEG region, which supported macrophage migration. Myosin IIA played a negative role in macrophage motility. Moreover, a developed cellular Potts model reproduced the experimental observations. These findings uncovered a new migratory behavior on non-adhesive surfaces in macrophages. One-Sentence SummaryMacrophages can migrate across non-adhesive surfaces that are absolute boundaries for other cell types.

cell biology↗

bioRxiv2022

All atom molecular dynamics simulation of the combinedeffects of different phospholipids and cholesterolcontents on electroporation

The electroporation mechanism could be related to the composition of the plasma membrane, and the combined effect of different phospholipids molecules and cholesterol contents on electroporation is rarely studied and concluded. In this paper, we applied all-atom molecular dynamics (MD) simulation to study the effects of phospholipids and cholesterol contents on bilayer membrane electroporation. The palmitoyl-oleoyl-phosphatidylcholine (POPC) model, palmitoyl-oleoyl-phosphatidylethanolamine (POPE) model and 1:1 mixed model of POPC and POPE called PEPC were three basic models. An electric field of 0.45 V/nm was applied to nine models including three basic models with cholesterol contents of 0%, 24%, and 40%. The interfacial water molecules moved under the electric field, and once the first water bridge formed, the rest of the water molecules would dramatically flood into the membrane. The simulation showed that a rapid rise in the Z component of the average dipole moment of interfacial water (Z-DM) indicated the occurrence of electroporation, and the same increment of Z-DM represented the similar change in the size of water bridge. With the same cholesterol content, the formation of the first water bridge was the most rapid in POPC model regarding the average electroporation time (tep), and the average tep of the PEPC model was close to that of the POPE model. We speculate that the difference in membrane thickness and initial hydrogen bonds of interfacial water affecting the average tep among different membrane composition. Our results reveal the influence of membrane composition on electroporation mechanism at the molecular level.

biochemistry↗

bioRxiv2022

Molecular dynamics study of phospholipid membrane electroporation induced by bipolar pulses with different intervals

In this study, PM-EP induced by bipolar pulses with different intervals was investigated by all-atom molecular dynamics simulation. Firstly, PM-EP was formed during the positive pulse of 2ns and 0.5V/nm, then the effects of various intervals of 0, 1, 5, 10ns on PM-EP evolution were investigated, and the dynamic changes of different degrees of PM-EP induced by following negative pulses of 2ns and 0.5V/nm were analyzed. The elimination of the PM-EP during the interval of bipolar pulses were determined and it was related to the degrees of PM-EP and the time of intervals, then the degrees of PM-EP at the end of the intervals were classified and quantitatively defined, namely, Resealing, Destabilizing and Retaining state. These three states appeared due to the combined effect of both the preceding positive pulse and the interval. Furthermore, the evolution of PM-EP in resealing state under negative pulses was similar to that of positive pulses as evidenced by EP formation time and degree of PM-EP, the destabilizing state had the same trends as the resealing state except that the re-electroporation of phospholipid membrane appeared faster and larger degree of EP obtained with the same pulse exposure time. Regarding the retaining state, the negative pulses enhanced PM-EP with more profound water bridges, which can be considered as the effect of electric field superposition. These results can improve our understanding of the fundamental mechanism of bipolar pulse-induced PM-EP. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/501059v1_ufig1.gif" ALT="Figure 1"> View larger version (87K): org.highwire.dtl.DTLVardef@9a1d36org.highwire.dtl.DTLVardef@1f3f6ccorg.highwire.dtl.DTLVardef@1d0068dorg.highwire.dtl.DTLVardef@5e1e2b_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIQuantitative and qualitative definition of the three states of the phospholipid membrane electroporation at the end of the intervals. C_LIO_LIClarification that the states of phospholipid membrane electroporation were generated due to the combined effect of positive pulses and intervals. C_LIO_LIQuantitative and qualitative comparison the evolution of the states of phospholipid membrane electroporation during the negative pulses. C_LI

biochemistry↗

bioRxiv2022

A low-cost and open-source solution to automate imaging and analysis of cyst nematode infection assays for Arabidopsis thaliana

BackgroundCyst nematodes are one of the major groups of plant-parasitic nematode, responsible for considerable crop losses worldwide. Improving genetic resources, and therefore resistant cultivars, is an ongoing focus of many pest management strategies. One of the major bottlenecks in identifying the plant genes that impact the infection, and thus the yield, is phenotyping. The current available screening method is slow, has unidimensional quantification of infection limiting the range of scorable parameters, and does not account for phenotypic variation of the host. The ever-evolving field of computer vision may be the solution for both the above-mentioned issues. To utilise these tools, a specialised imaging platform is required to take consistent images of nematode infection in quick succession. ResultsHere, we describe an open-source, easy to adopt, imaging hardware and trait analysis software method based on a pre-existing nematode infection screening method in axenic culture. A cost-effective, easy-to-build and -use, 3D-printed imaging device was developed to acquire images of the root system of Arabidopsis thaliana infected with the cyst nematode Heterodera schachtii, replacing costly microscopy equipment. Coupling the output of this device to simple analysis scripts allowed the measurement of some key traits such as nematode number and size from collected images, in a semi-automated manner. Additionally, we used this combined solution to quantify an additional trait, root area before infection, and showed both the confounding relationship of this trait on nematode infection and a method to account for it. ConclusionTaken together, this manuscript provides a low-cost and open-source method for nematode phenotyping that includes the biologically relevant nematode size as a scorable parameter, and a method to account for phenotypic variation of the host. Together these tools highlight great potential in aiding our understanding of nematode parasitism.

plant biology↗

bioRxiv2022

Oscillatory mechanisms of intrinsic brain networks

Neuroimaging studies of hemodynamic fluctuations have shown specific network-based organization of the brain at rest, yet the neurophysiological underpinning of these networks in human brain remain unclear. Here, we recorded resting-state activities of neuronal populations in the key regions of default mode network (DMN, posterior cingulate cortex and medial prefrontal cortex), frontoparietal network (FPN, dorsolateral prefrontal cortex and inferior parietal lobule), and salience network (SN, anterior insula and dorsal anterior cingulate cortex) from 42 human participants using intracranial electroencephalogram (iEEG). We observed stronger within-network connectivity of the DMN, FPN and SN in broadband iEEG power, stronger phase synchronization within the DMN across theta and alpha bands, and weaker phase synchronization within the FPN in delta, theta and alpha band. We also found positive power correlations in high frequency band (70-170Hz) and negative power correlations in alpha and beta band for FPN-DMN and FPN-SN. Robust negative correlations in DMN-SN were found in alpha, beta and gamma band. These findings provide intracranial electrophysiological evidence in support of the network model for intrinsic organization of human brain and shed light on the way how the brain networks communicate at rest.

neuroscience↗

bioRxiv2022

Zbtb14 regulates monocyte and macrophage development through inhibiting pu.1 expression in zebrafish

Macrophages and their precursor cells, monocytes, are the first line of defense of the body against foreign pathogens and tissue damage. Although the origins of macrophages are diverse, some common transcription factors (such as PU.1) are required to ensure proper development of monocytes/macrophages. Here we report that the deficiency of zbtb14, a transcription repressor gene belonging to ZBTB family, leads to an aberrant expansion of monocyte/macrophage population in zebrafish. Mechanistically, Zbtb14 functions as a negative regulator of pu.1, and SUMOylation on a conserved lysine is essential for the repression activity of Zbtb14. Moreover, a serine to phenylalanine mutation found in an acute myeloid leukemia (AML) patient could target ZBTB14 protein to autophagic degradation. Hence, ZBTB14 is a newly identified gene implicated in both normal and malignant myelopoiesis.

developmental biology↗