Condensate remodeling reorganizes innate SS18 in synovial sarcomagenesis.

SS18-SSX onco-fusion protein formed through aberrant chromosomal translocation t (X, 18; p11, q11), is the hallmark and plays a critical role in synovial sarcomagenesis. The recent works indicated that both the pathological SS18-SSX tumorigenic fusion and the corresponding intrinsic physiological SS18 protein can form condensates but appear to have disparate properties. The underlying regulatory mechanism and the consequent biological significance remain largely unknown.

TRPM2 as a conserved gatekeeper determines the vulnerability of DA neurons by mediating ROS sensing and calcium dyshomeostasis.

Different dopaminergic (DA) neuronal subgroups exhibit distinct vulnerability to stress, while the underlying mechanisms are elusive. Here we report that the transient receptor potential melastatin 2 (TRPM2) channel is preferentially expressed in vulnerable DA neuronal subgroups, which correlates positively with aging in Parkinson's Disease (PD) patients. Overexpression of human TRPM2 in the DA neurons of C.

Single-cell RNA sequencing reveals the developmental program underlying proximal-distal patterning of the human lung at the embryonic stage.

The lung is the primary respiratory organ in human, in which the proximal airway and the distal alveoli are responsible for air conduction and gas exchange, respectively. However, the regulation of proximal-distal patterning at the embryonic stage of human lung development is largely unknown. Here we investigated the early lung development of human embryos at weeks 4-8 post fertilization (Carnegie stages 12-21) using single-cell RNA sequencing, and obtained a transcriptomic atlas of 169,686 cells.

Comprehensive Perspectives on Experimental Models for Parkinson's Disease.

Parkinson's disease (PD) ranks second among the most common neurodegenerative diseases, characterized by progressive and selective loss of dopaminergic neurons. Various cross-species preclinical models, including cellular models and animal models, have been established through the decades to study the etiology and mechanism of the disease from cell lines to nonhuman primates. These models are aimed at developing effective therapeutic strategies for the disease.

Azoramide protects iPSC-derived dopaminergic neurons with PLA2G6 D331Y mutation through restoring ER function and CREB signaling.

The endoplasmic reticulum (ER)-stress-induced cascade events are implicated in Parkinson's disease (PD). The discovery of drug candidates to protect dopaminergic (DA) neurons from ER-stress-induced oxidative damage is important to resolve the pathological aspects of PD and modify its progress. In this study, we found that a recently identified unfolded protein response (UPR) modulator, azoramide, showed protective effects on patient induced pluripotent stem cells-derived midbrain DA neurons with the homozygous phospholipase A2 group 6 (PLA2G6) D331Y mutant.

Using induced pluripotent stem cells for modeling Parkinson's disease.

Parkinson's disease (PD) is an age-related neurodegenerative disease caused by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. As DA neurons degenerate, PD patients gradually lose their ability of movement. To date no effective therapies are available for the treatment of PD and its pathogenesis remains unknown.

Hydroxyurea Facilitates Manifestation of Disease Relevant Phenotypes in Patients-Derived IPSCs-Based Modeling of Late-Onset Parkinson's Disease.

Induced pluripotent stem cells (iPSCs)-derived dopaminergic neurons might be reset back to the fetal state due to reprogramming. Thus, it is a compelling challenge to reliably and efficiently induce disease phenotypes of iPSCs-derived dopaminergic neurons to model late-onset Parkinson's disease (PD). Here, we applied a small molecule, hydroxyurea (HU), to promote the manifestation of disease relevant phenotypes in iPSCs-based modeling of PD.

Presenilin 1 deficiency suppresses autophagy in human neural stem cells through reducing γ-secretase-independent ERK/CREB signaling.

Autophagy impairment is commonly implicated in the pathological characteristic of Alzheimer's disease (AD). Presenilin 1 (PS1) expression in human brain gradually decreases with age and its mutations account for the most common cases of early-onset familial Alzheimer's disease (FAD). The dominant autophagy phenotypes occur in PS1-knockout and PS1 mutant neurons; it is still unknown whether PS1 deficiency causes serious autophagy impairment in neural stem cells (NSCs).

Roles of Nitric Oxide Synthase Isoforms in Neurogenesis.

Nitric oxide (NO), a free radical gas, acts as a neurotransmitter or neuromodulator in the central nervous system (CNS). It has been widely explored as a mediator of neuroinflammation, neuronal damages, and neurodegeneration at its pathological levels. Recently, increasing evidence suggests that NO plays key roles in mediating adult neurogenesis, the process of neural stem cells (NSCs) to generate newborn neurons for replacing damaged neurons or maintaining the function of the brain.