Biology subjects

Pilapong, C.

Publications and source records attributed to Pilapong, C..

3 recordsLinked to original sources

bioRxiv2025

Generation of Neural Stem/Progenitor-like Cells from Cultured Human Peripheral Blood Mononuclear Cells combined with Cannabidiol

Recent advances in chemical reprogramming with small molecule combination have enabled the direct conversion of somatic cells into different cell lineages without genetic modification. This study aimed to investigate reprogramming and differentiation capacity of peripheral blood mononuclear cells (PBMCs) after treating with only a single small molecule, cannabidiol (CBD). The differentiated reprogrammed cells exhibited high expression of neuronal stem/progenitor cell (NSPCs) markers without pluripotency markers, suggesting cellular identity was switched to NSPCs via direct reprogramming. Transcriptomics and proteomic analyses of the differentiated reprogrammed cells showed the remarkable expression of genes specific to NSPCs and endocannabinoid system along with regenerative parameters and morphogenesis. Unexpectedly, we have found that PBMCs may inherently possess certain levels of plasticity or potency, possibly through dedifferentiation or transdifferentiation mechanisms. Our findings convey the idea that CBD together with intrinsic plasticity of PBMCs might be able to induce the transdifferentiation of PBMCs.

cell biology↗

bioRxiv2024

Storage and transport of labile iron is mediated by lysosomes in axons and dendrites of hippocampal neurons

Iron dyshomeostasis in neurons, involving iron accumulation and abnormal redox balance, is implicated in neurodegeneration. In particular, labile iron, a highly reactive pool of intracellular iron, plays a prominent role in iron-induced neurological damage. However, the mechanisms governing the detoxification and transport of labile iron within neurons are not fully understood. This study investigates the storage and transport of labile ferrous iron Fe(II) in cultured primary rat hippocampal neurons. Iron distribution was studied using live cell confocal microscopy with a selective labile Fe(II) fluorescent dye, and synchrotron X-ray fluorescence microscopy (SXRF) for total iron distribution. Fluorescent labelling of the axon initial segment and of lysosomes allowed iron distribution to be correlated with these subcellular compartments. The results show that labile Fe(II) is stored in lysosomes within somas, axons and dendrites and that lysosomal labile Fe(II) is transported retrogradely and anterogradely along axons and dendrites. In addition, we have developed a methodological workflow to quantify labile Fe(II) relative to total iron in neurites. This method is based on correlative imaging of fluorescence microscopy of labile Fe(II) combined with quantitative elemental mapping of total iron by SXRF. Quantitative analysis revealed that after Fe(II) exposure, lysosomal Fe(II) accounts for a small but significant percentage of the total iron content in neurites. These result suggest that after exposure to labile Fe(II), iron is mainly present in a non-reactive form in neurons, while the smaller fraction of reactive labile Fe(II) is stored in lysosomes and can be transported along dendrites and axons.

neuroscience↗

bioRxiv2023

The Role of Labile Iron on Brain Proteostasis; Could it be an Early Event of Neurodegenerative Disease?

Iron deposits in the brain are a natural consequence of aging. Iron accumulation, especially in the form of labile iron, can trigger a cascade of adverse effects, eventually leading to neurodegeneration and cognitive decline. Aging also increases the dysfunction of cellular proteostasis. The question of whether iron alters proteostasis is now being pondered. Herein, we investigated the effect of ferric citrate, considered as labile iron, on various aspects of proteostasis of neuronal cell lines, and also established an animal model having a labile iron diet in order to evaluate proteostasis alteration in the brain along with behavioral effects. According to an in vitro study, labile iron was found to activate lysosome formation but inhibits lysosomal clearance function. Furthermore, the presence of labile iron can alter autophagic flux and can also induce the accumulation of protein aggregates. RNA-sequencing analysis further reveals the upregulation of various terms related to proteostasis along with neurodegenerative disease-related terms. According to an in vivo study, a labile iron-rich diet does not induce iron overload conditions and was not detrimental to the behavior of male Wistar rats. However, an iron-rich diet can promote iron accumulation in a region-dependent manner, particularly in the cortex. By staining for autophagic markers and misfolding proteins in the cerebral cortex, the iron-rich diet was actually found to alter autophagy and induce an accumulation of misfolding proteins. These findings emphasize the importance of labile iron on brain cell proteostasis, which could be implicated in developing of neurological diseases. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=85 SRC="FIGDIR/small/567981v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@442c01org.highwire.dtl.DTLVardef@1a50219org.highwire.dtl.DTLVardef@2cc997org.highwire.dtl.DTLVardef@66ec15_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗