Biology subjects

Hidalgo, I.

Publications and source records attributed to Hidalgo, I..

7 recordsLinked to original sources

bioRxiv2025

Rapid and efficient generation of human oligodendrocytes myelinating adult human cortical neurons

Intracerebral transplantation of stem cell-derived oligodendrocytes (OLs) is a promising strategy for repairing demyelinated human brain tissue, the main hallmark of white-matter disorders. However, several challenges hinder clinical translation, including slow or inefficient production of human OLs with current protocols, and difficulty in generating pure OL grafts capable of remyelinating injured neural circuits. Here, we present a robust, highly reproducible method for the rapid and efficient production of human OLs from human induced pluripotent stem cell derived long-term neuroepithelial-like stem (lt-NES) cells. Induced expression of the lineage-defining transcription factors SOX10 and OLIG2 in lt-NES cells is sufficient to generate a population of 80% OLs within 7 days. Importantly, these cells survive, differentiate and form functional OL-exclusive grafts when transplanted into adult human brain slices ex vivo, constituting the first demonstration that an OL-exclusive graft with robust myelination capacity can be generated in a clinically relevant allogeneic environment. This advance marks a significant step towards the clinical application of oligodendrocyte replacement therapy for human demyelinating disorders.

neuroscience↗

bioRxiv2024

Medium-dose irradiation impairs long-term hematopoietic stem cell functionality and hematopoietic recovery to cytotoxic stress

Irradiation and 5-fluorouracil (5-FU) are widely utilized tools in hematopoietic research to generate myeloablation and assess blood recovery dynamics. A comprehensive understanding of their effects on the hematopoietic system is essential for optimizing therapeutic strategies, refining experimental models to modulate hematotoxicity, and interpreting research outcomes. Despite their widespread application, the long-term hematopoietic impacts of irradiation and 5-FU, particularly on hematopoietic stem cells (HSCs), remain incompletely characterized. In this study, we therefore examined the long-term effects of 2 Gy medium-dose ionizing radiation (MDIR) and 150 mg/kg 5-FU on HSCs and the hematopoietic systems resilience to subsequent cytotoxic stress in mice. Our findings demonstrate that MDIR, but not 5-FU, induces sustained impairments in HSC function and results in the selective depletion of MHC class II- HSCs - a subset characterized by high self-renewal potential. Furthermore, MDIR significantly compromised hematopoietic recovery following a subsequent 5-FU challenge, as evidenced by notably reduced platelet and red blood cell (RBC) counts during the critical recovery phase. These findings highlight the distinct and persistent impacts of MDIR and 5-FU on HSCs and hematopoietic function, revealing crucial differences in their mechanisms of action and long-term consequences on the hematopoietic system.

cell biology↗

bioRxiv2023

Nitric Oxide controls shoot meristem activity via regulation of DNA methylation

Despite the importance of Nitric Oxide (NO) as signaling molecule in both plant and animal development1-7, the regulatory mechanisms downstream of NO remain largely unclear. Here, we show that NO is involved in Arabidopsis shoot stem cell control via modifying expression and activity of ARGONAUTE 4 (AGO4), a core component of the RNA directed DNA Methylation (RdDM) pathway. Mutations in components of the RdDM pathway cause meristematic defects, and reduce responses of the stem cell system to NO signaling. Importantly, we found that the stem cell inducing WUSCHEL transcription factor directly interacts with AGO4 in an NO dependent manner, explaining how these two signaling systems may converge to modify DNA methylation patterns. Taken together, our results reveal that NO signaling plays an important role in controlling plant stem cell homeostasis via the regulation of de novo DNA methylation.

plant biology↗

bioRxiv2023

Oligodendrocytes in human iPS cell-derived cortical grafts remyelinate adult rat and human cortical neurons

Neuronal loss and axonal demyelination underlie long-term functional impairments in patients affected by brain disorders such as ischemic stroke. Stem cell-based approaches reconstructing and remyelinating brain neural circuitry, leading to recovery, are highly warranted. Here we demonstrate the in vitro and in vivo production of myelinating oligodendrocytes from a human induced pluripotent stem (iPS) cell-derived long-term neuroepithelial stem (lt-NES) cell line, which also gives rise to neurons with the capacity to integrate into stroke-injured, adult rat cortical networks. Most importantly, the generated oligodendrocytes survive and form myelin ensheathing human axons in the host tissue after grafting onto adult human cortical organotypic cultures. This lt-NES cell line is the first human stem cell source that after intracerebral delivery can repair both injured neural circuitries and demyelinated axons. Our findings provide supportive evidence for the potential future use of human iPS cell-derived cell lines to promote effective clinical recovery following brain injuries.

neuroscience↗

bioRxiv2022

The male mouse meiotic cilium emanates from the mother centriole at zygotene prior to centrosome duplication

Cilia are hair-like projections of the plasma membrane with an inner microtubule skeleton known as axoneme. Motile cilia and flagella beat to displace extracellular fluids, playing important roles in the airways and reproductive system, among others. Instead, primary cilia function as cell type-dependent sensory organelles, detecting chemical, mechanical or optical signals from the extracellular environment. Cilia dysfunction is associated with genetic diseases called ciliopathies, and with some types of cancer. Cilia have been recently identified in zebrafish gametogenesis as an important regulator of the bouquet conformation and recombination. However, there is very little information about the structure and functions of cilia in mammalian meiosis. Here we describe the presence of cilia in male mouse meiotic cells. These solitary cilia form transiently in 20% of zygotene spermatocytes and reach considerable lengths (up to 15 m). CEP164 and CETN3 localization studies indicate that these cilia emanate from the mother centriole, prior to centrosome duplication. In addition, the study of telomeric TFR2 suggests that these cilia are not directly related to the bouquet conformation during early male mouse meiosis. Instead, based on TEX14 labeling of intercellular bridges in spermatocyte cysts, we suggest that mouse meiotic cilia may have sensory roles affecting cyst function during prophase I.

cell biology↗

bioRxiv2022

Opposite polarity programs regulate asymmetric subsidiary cell divisions in grasses

Grass stomata recruit lateral subsidiary cells (SCs), which are key to the unique stomatal morphology and the efficient plant-atmosphere gas exchange in grasses. Subsidiary mother cells (SMCs) strongly polarise before an asymmetric division forms a SC. Yet apart from a proximal polarity module that includes PANGLOSS1 (PAN1) and guides nuclear migration, little is known regarding the developmental processes that form SCs. Using the genetic model grass Brachypodium distachyon, we identified BdPOLAR, which forms a novel, distal polarity domain in SMCs that is reciprocal to the proximal PAN1 domain. Both polarity domains are required for the formative SC division yet exhibit distinct roles in regulating pre-mitotic nuclear migration and SMC division plane orientation, respectively. Nonetheless, the domains are linked as the proximal domain controls polarisation of the distal domain. In summary, we identified two opposing polarity domains that coordinate the SC division, a process crucial for grass stomatal physiology.

plant biology↗

bioRxiv2020

Dissection of PRC1 and PRC2 recruitment in Arabidopsis connects EAR repressome to PRC2 anchoring

PcG complexes ensure that every cell in an organism expresses the genes needed at a particular stage, time or condition. However, it is still not fully understood how PRC1 and PRC2 are recruited to target genes in plants. Recent results in Arabidopsis support that PRC2 recruitment is mediated by different TFs. However, it is unclear how all these TFs interact with PRC2 and whether they can also recruit PRC1 activity. Here, by using a system to in vivo bind selected factors to a synthetic promoter lacking the complexity of PcG target promoters, we show that while VAL1 binding recapitulates PRC1 and PRC2 marking, the binding of other TFs only render PRC2 marking. Interestingly, all these TFs contain an EAR domain that acts as docking point for PRC2 and HDACs, connecting two different repressive mechanisms. Furthermore, we show that different TFs act synergistically in PRC2 anchoring to maintain a long-term repression.

plant biology↗