Biology subjects

Moraleda, J. M.

Publications and source records attributed to Moraleda, J. M..

3 recordsLinked to original sources

bioRxiv2023

The nuclei of human adult stem cells can move within the cell and generate cellular protrusions to contact other cells

Despite a considerable interest in understanding the mechanisms regulating nucleus structure, chromatin organization and nuclear positioning over decades, the exact significance of the variety of morphologies and positioning that cell nuclei can adopt and their relationship in cellular function is still far from being clearly understood. In this study, we examined the functional significance of the variety of morphologies and positioning that cell nuclei of human bone marrow-derived mesenchymal stem cells can adopt during neural-like differentiation. Here, we show that after neural induction, human bone marrow-derived mesenchymal stem cells enter an intermediate cellular state in which the nuclei are observed to be able to move within the cells, switching shapes and positioning and even generating cellular protrusions as they attempt to contact the cells around them. These findings suggest that changes in nuclear positioning are due to the fact that human cell nuclei somehow sensing their environment.

cell biology↗

bioRxiv2022

Binucleated cells generated by nuclear movement during neural transdifferentiation from human bone marrow-derived mesenchymal cells

Although it has been reported that bone marrow-derived cells (BMDCs) can transdifferentiate into neural cells, the findings are considered unlikely. It has been argued that the rapid neural transdifferentiation of BMDCs reported in culture studies is actually due to cytotoxic changes induced by the media. While transplantation studies indicated that BMDCs can form new neurons, it remains unclear whether the underlying mechanism is transdifferentiation or BMDCs-derived cell fusion with the existing neuronal cells. Cell fusion has been put forward to explain the presence of gene-marked binucleated neurons after gene-marked BMDCs transplantation. In the present study, we demostrated that human BMDCs can rapidly adopt a neural-like morphology through active neurite extension and binucleated human BMDCs can form with independence of any cell fusion events. We also showed that BMDCs neural transdifferentiation involves the formation of intermediate cells which can then redifferentiate into neural-like cells, redifferentiate back to the mesenchymal fate or even repeatedly switch lineages without cell division. Furthermore, we have discovered that nuclei from intermediate cells rapidly move within the cell, adopting different morphologies and even forming binucleated cells. Therefore, our results provide a stronger basis for rejecting the idea that BMDCs neural transdifferentiation is merely an artefact.

neuroscience↗

bioRxiv2021

Differentiation of human adult-derived stem cells towards a neural lineage involves a de-differentiation event prior to re-differentiation to neural phenotypes

Although it has been reported that mesenchymal stem cells isolated from adult tissues can be induced to overcome their mesenchymal fate and transdifferentiate into neural cells, the findings and their interpretation have been challenged. The main argument against this process is that the cells rapidly adopt neuron-like morphologies through retraction of the cytoplasm rather than active neurite extension. In this study, we examined the sequence of biological events during neural differentiation of human periodontal ligament-derived stem cells (hPDLSCs), human bone marrow-derived stem cells (hBMSCs) and human dental pulp-derived stem cells (hDPSCs) by time-lapse microscopy. We have demonstrated that hPDLSCs, hBMSCs and hDPSCs can directly differentiate into neuron-like cells without passing through a mitotic stage and that they shrink dramatically and change their morphology to that of neuron-like cells through active neurite extension. Furthermore, we observed micronuclei movement and transient cell nuclei lobulation concurrent to in vitro neurogenesis from hBMSCs and hDPSCs. Our results demonstrate that the differentiation of hPDLSCs, hBMSCs and hDPSCs towards a neural lineage occurs through a de-differentiation step followed by re-differentiation to neural phenotypes, and therefore we definitively confirm that the rapid acquisition of the neural phenotype is via a differentiation trait.

neuroscience↗