Cell delamination is a conserved morphogenetic process important for the generation of cell diversity and maintenance of tissue homeostasis. Here, we used
embryonic neuroblasts as a model to study ...the apical constriction process during cell delamination. We observe dynamic myosin signals both around the cell adherens junctions and underneath the cell apical surface in the neuroectoderm. On the cell apical cortex, the nonjunctional myosin forms flows and pulses, which are termed medial myosin pulses. Quantitative differences in medial myosin pulse intensity and frequency are crucial to distinguish delaminating neuroblasts from their neighbors. Inhibition of medial myosin pulses blocks delamination. The fate of a neuroblast is set apart from that of its neighbors by Notch signaling-mediated lateral inhibition. When we inhibit Notch signaling activity in the embryo, we observe that small clusters of cells undergo apical constriction and display an abnormal apical myosin pattern. Together, these results demonstrate that a contractile actomyosin network across the apical cell surface is organized to drive apical constriction in delaminating neuroblasts.
The MS 6.9 Menyuan earthquake in Qinghai Province, west China is the largest earthquake by far in 2022. The earthquake occurs in a tectonically active region, with a background b-value of 0.87 within ...100 km of the epicenter that we derived from the unified catalog produced by China Earthquake Networks Center since late 2008. Field surveys have revealed surface ruptures extending 22 km along strike, with a maximum ground displacement of 2.1 m. We construct a finite fault model with constraints from InSAR observations, which showed multiple fault segments during the Menyuan earthquake. The major slip asperity is confined within 10 km at depth, with the maximum slip of 3.5 m. Near real-time back-projection results of coseismic radiation indicate a northwest propagating rupture that lasted for ∼10 s. Intensity estimates from the back-projection results show up to a Mercalli scale of IX near the ruptured area, consistent with instrumental measurements and the observations from the field surveys. Aftershock locations (up to January 21, 2022) exhibit two segments, extending to ∼20 km in depth. The largest one reaches MS 5.3, locating near the eastern end of the aftershock zone. Although the location and the approximate magnitude of the mainshock had been indicated by previous studies based on paleoearthquake records and seismic gap, as well as estimated stressing rate on faults, significant surface-breaching rupture leads to severe damage of the high-speed railway system, which poses a challenge in accurately assessing earthquake hazards and risks, and thus demands further investigations of the rupture behaviors for crustal earthquakes.
•We present a finite fault model of the 2022 MS 6.9 Menyuan earthquake with constraints from InSAR data, which showed a maximum slip of ~3.5 m and clear surface rupture.•A near real-time intensity map is generated from back-project results, showing great agreement with what was established through field surveys.•We conduct double-difference relocations of aftershocks in the first two weeks following the mainshock, which distribute in two segments and extend to 20 km in depth.•Statistical results of the Menyuan earthquakes suggest a mainshock-aftershock type sequence.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Histone variants, present in various cell types and tissues, are known to exhibit different functions. For example, histone H3.3 and H2A.Z are both involved in gene expression regulation, whereas ...H2A.X is a specific variant that responds to DNA double-strand breaks. In this study, we characterized H4G, a novel hominidae-specific histone H4 variant. We found that H4G is expressed in a variety of human cell lines and exhibit tumor-stage dependent overexpression in tissues from breast cancer patients. We found that H4G localized primarily to the nucleoli of the cell nucleus. This localization was controlled by the interaction of the alpha-helix 3 of the histone fold motif with a histone chaperone, nucleophosmin 1. In addition, we found that modulating H4G expression affects rRNA expression levels, protein synthesis rates and cell-cycle progression. Our data suggest that H4G expression alters nucleolar chromatin in a way that enhances rDNA transcription in breast cancer tissues.
The heterogeneity of functional cardiomyocytes arises during heart development, which is essential to the complex and highly coordinated cardiac physiological function. Yet the biological and ...physiological identities and the origin of the specialized cardiomyocyte populations have not been fully comprehended. Here we report a previously unrecognised population of cardiomyocytes expressing Dbhgene encoding dopamine beta-hydroxylase in murine heart. We determined how these myocytes are distributed across the heart by utilising advanced single-cell and spatial transcriptomic analyses, genetic fate mapping and molecular imaging with computational reconstruction. We demonstrated that they form the key functional components of the cardiac conduction system by using optogenetic electrophysiology and conditional cardiomyocyte Dbh gene deletion models. We revealed their close relationship with sympathetic innervation during cardiac conduction system formation. Our study thus provides new insights into the development and heterogeneity of the mammalian cardiac conduction system by revealing a new cardiomyocyte population with potential catecholaminergic endocrine function.
Abstract
Placenta plays essential role in successful pregnancy, as the most important organ connecting and interplaying between mother and fetus. However, the cellular characteristics and molecular ...interaction of cell populations within the fetomaternal interface is still poorly understood. Here, we surveyed the single-cell transcriptomic landscape of human full-term placenta and revealed the heterogeneity of cytotrophoblast cell (CTB) and stromal cell (STR) with the fetal/maternal origin consecutively localized from fetal section (FS), middle section (Mid_S) to maternal section (Mat_S) of maternal–fetal interface. Then, we highlighted a subpopulation of CTB, named trophoblast progenitor-like cells (TPLCs) existed in the full-term placenta and mainly distributed in Mid_S, with high expression of a pool of putative cell surface markers. Further, we revealed the putative key transcription factor
PRDM6
that might promote the differentiation of endovascular extravillous trophoblast cells (enEVT) by inhibiting cell proliferation, and down-regulation of
PRDM6
might lead to an abnormal enEVT differentiation process in PE. Together, our study offers important resources for better understanding of human placenta and stem cell-based therapy, and provides new insights on the study of tissue heterogeneity, the clinical prevention and control of PE as well as the maternal–fetal interface.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The brain is spatially organized and contains unique cell types, each performing diverse functions and exhibiting differential susceptibility to neurodegeneration. This is exemplified in Parkinson’s ...disease with the preferential loss of dopaminergic neurons of the substantia nigra pars compacta. Using a Parkinson’s transgenic model, we conducted a single-cell spatial transcriptomic and dopaminergic neuron translatomic analysis of young and old mouse brains. Through the high resolving capacity of single-cell spatial transcriptomics, we provide a deep characterization of the expression features of dopaminergic neurons and 27 other cell types within their spatial context, identifying markers of healthy and aging cells, spanning Parkinson’s relevant pathways. We integrate gene enrichment and genome-wide association study data to prioritize putative causative genes for disease investigation, identifying CASR as a regulator of dopaminergic calcium handling. These datasets represent the largest public resource for the investigation of spatial gene expression in brain cells in health, aging, and disease.
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•Single-cell spatial transcriptomic study of mouse brain expression in health, age, and disease•Deep characterization of dopaminergic expression using Stereo-seq and TRAP•SpatialBrain: resource for expression data exploration
Kilfeather et al. showcase a single-cell spatial transcriptomic study of mouse brain spanning 29 cell types. They describe gene expression changes in health, age, and a model of Parkinson’s disease. Using TRAP, they further interrogate dopaminergic expression and demonstrate a role for CASR in modulating calcium handling.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The 2022 MS 6.8 Luding earthquake is the strongest earthquake in Sichuan Province, Western China, since the 2017 MS 7.0 Jiuzhaigou earthquake. It occurred on the Moxi fault in the southeastern ...segment of the Xianshuihe fault, a tectonically active and mountainous region with severe secondary earthquake disasters. To better understand the seismogenic mechanism and provide scientific support for future hazard mitigation, we summarize the preliminary results of the Luding earthquake, including seismotectonic background, seismicity and mainshock source characteristics and aftershock properties, and direct and secondary damage associated with the mainshock. The peak ground displacements in the NS and EW directions observed by the nearest GNSS station SCCM are ∼35 mm and ∼55 mm, respectively, resulting in the maximum coseismic dislocation of 20 mm along the NWW direction, which is consistent with the sinistral slip on the Xianshuihe fault. Back-projection of teleseismic P waves suggest that the mainshock rupture propagated toward south-southeast. The seismic intensity of the mainshock estimated from the back-projection results indicates a Mercalli scale of VIII or above near the ruptured area, consistent with the results from instrumental measurements and field surveys. Numerous aftershocks were reported, with the largest being MS 4.5. Aftershock locations (up to September 18, 2022) exhibit 3 clusters spanning an area of 100 km long and 30 km wide. The magnitude and rate of aftershocks decreased as expected, and the depths became shallower with time. The mainshock and two aftershocks show left-lateral strike-slip focal mechanisms. For the aftershock sequence, the b-value from the Gutenberg-Richter frequency-magnitude relationship, h-value, and p-value for Omori’s law for aftershock decay are 0.81, 1.4, and 1.21, respectively, indicating that this is a typical mainshock-aftershock sequence. The low b-value implies high background stress in the hypocenter region. Analysis from remote sensing satellite images and UAV data shows that the distribution of earthquake-triggered landslides was consistent with the aftershock area. Numerous small-size landslides with limited volumes were revealed, which damaged or buried the roads and severely hindered the rescue process.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mesenchymal stem/stromal cells (MSCs) show tremendous potential for regenerative medicine due to their self-renewal, multi-differentiation and immunomodulatory capabilities. Largely studies had ...indicated conventional tissue-derived MSCs have considerable limited expandability and donor variability which hinders further application. Induced pluripotent stem cell (iPSCs)-derived MSCs (iMSCs) have created exciting source for standardized cellular therapy. However, the cellular and molecular differences between iMSCs and the cognate tissue-derived MSCs remains poorly explored. In this study, we first successfully reprogrammed human umbilical cords-derived mesenchymal stem/stromal cells (UMSCs) into iPSCs by using the cocktails of mRNA. Subsequently, iPSCs were further differentiated into iMSCs in xeno-free induction medium. Then, iMSCs were compared with the donor matched UMSCs by assessing proliferative state, differentiation capability, immunomodulatory potential through immunohistochemical analysis, flow cytometric analysis, transcriptome sequencing analysis, and combine with coculture with immune cell population. The results showed that iMSCs exhibited high expression of MSCs positive-makers CD73, CD90, CD105 and lack expression of negative-maker cocktails CD34, CD45, CD11b, CD19, HLA-DR; also successfully differentiated into osteocytes, chondrocytes and adipocytes. Further, the iMSCs were similar with their parental UMSCs in cell proliferative state detected by the CCK-8 assay, and in cell rejuvenation state assessed by β-Galactosidase staining and telomerase activity related mRNA and protein analysis. However, iMSCs exhibited similarity to resident MSCs in Homeobox (Hox) genes expression profile and presented better neural differentiation potential by activation of NESTIN related pathway. Moreover, iMSCs owned enhanced immunosuppression capacity through downregulation pools of pro-inflammatory factors, including IL6, IL1B etc. and upregulation anti-inflammatory factors NOS1, TGFB etc. signals. In summary, our study provides an attractive cell source for basic research and offers fundamental biological insight of iMSCs-based therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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