Biology subjects

Riquelme, R.

Publications and source records attributed to Riquelme, R..

4 recordsLinked to original sources

bioRxiv2024

Longitudinal transcriptional changes reveal genes from the natural killer cell-mediated cytotoxicity pathway as critical players underlying COVID-19 progression

Patients present a wide range of clinical severities in response SARS-CoV-2 infection, but the underlying molecular and cellular reasons why clinical outcomes vary so greatly within the population remains unknown. Here, we report that negative clinical outcomes in severely ill patients were associated with divergent RNA transcriptome profiles in peripheral immune cells compared with mild cases during the first weeks after disease onset. Protein-protein interaction analysis indicated that early-responding cytotoxic NK cells were associated with an effective clearance of the virus and a less severe outcome. This innate immune response was associated with the activation of select cytokine-cytokine receptor pathways and robust Th1/Th2 cell differentiation profiles. In contrast, severely ill patients exhibited a dysregulation between innate and adaptive responses affiliated with divergent Th1/Th2 profiles and negative outcomes. This knowledge forms the basis of clinical triage that may be used to preemptively detect high-risk patients before life-threatening outcomes ensue. Highlights- Mild COVID-19 patients displayed an early transcriptional commitment with NK cell function, whereas severe patients do so with neutrophil function. - The identified co-expressed genes give insights into a coordinated transcriptional program of NK cell cytotoxic activity being associated with mild patients. - Key checkpoints of NK cell cytotoxicity that were enriched in mild patients include: KLRD1, CD247, and IFNG. - The early innate immune response related to NK cells connects with the Th1/Th2 adaptive immune responses, supporting their relevance in COVID-19 progression.

immunology↗

bioRxiv2023

Carbon Sequestration in Soils below Seaweed Farms

The hypothesis that seaweed farming contributes to carbon burial below the farms was tested by quantifying burial rates in 20 seaweed farms distributed globally, ranging from 2 to 300 years in operation and from 1 ha to 15,000 ha in size. This involved combining analyses of organic carbon density with sediment accumulation rate in sediments below seaweed farms relative to reference sediments beyond the farm and/or prior to the farm operation. One in every four farms sampled was set over environments that export, rather than retain materials. For the farms that were placed over depositional environments, where sediment accumulation could be quantified, the thickness of sediment layers and stocks of carbon accumulated below the farms increased with farm age, reaching 140 ton C ha-1 for the oldest farm, and tended to exceed those in reference sediments beyond the farm and/or prior to the operation of the farms. Organic carbon burial rates in the farm sediments averaged ({+/-} SE) 1.87 {+/-} 0.73 ton CO2 equivalent (CO2-eq) ha-1 year-1 (median 0.83, range 0.10 - 8.99 ton CO2-eq ha-1 year-1), twice the average ({+/-} SE) burial rate in reference sediments (0.90 {+/-} 0.27, median 0.64, range 0.10-3.00 ton CO2-eq ha-1 year-1), so that the excess organic carbon burial attributable to the seaweed farms averaged 1.06 {+/-} 0.74 ton CO2-eq ha-1 year-1 (median 0.09, range -0.13-8.10 ton CO2-eq ha-1 year-1). This first direct quantification of carbon burial in sediments below seaweed farms confirms that, when placed over depositional environments, seaweed farming tend to sequester carbon in the underlying sediments, but do so at widely variable rates, increasing with farm yield.

ecology↗

bioRxiv2021

Transcription factor induction of vascular blood stem cell niches in vivo

The hematopoietic niche is a supportive microenvironment comprised of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses, we define a conserved gene expression signature and cis-regulatory landscape unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code involving members of the Ets, Sox and Nuclear Hormone Receptor families that is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche.

developmental biology↗

bioRxiv2017

Generation of Mouse-Zebrafish Hematopoietic Tissue Chimeric Embryos for Hematopoiesis and Host-Pathogen Interaction Studies

Xenografts of the hematopoietic system are extremely useful as disease models and for translational research. Zebrafish xenografts have been widely used to monitor blood cancer cell dissemination and homing due to the optical clarity of embryos and larvae, which allow unrestricted in vivo visualization of migratory events. To broaden the scope of xenotransplantation studies in zebrafish, we have developed a technique that transiently generates hematopoietic tissue chimeras by transplanting murine bone marrow cells into zebrafish blastulae. This procedure leads to mammalian cell integration into the fish developmental hematopoietic program. Monitoring zebrafish chimeras at different time points post fertilization using in vivo time-lapse and confocal imaging showed murine cell co-localization with developing primitive and definitive hematopoietic tissues, intravasation into fish circulation, and dynamic hematopoietic cell-vascular endothelial and hematopoietic cell-niche interactions. Immunohistochemistry assays performed in chimeric animals showed that, after engraftment, murine cells expressed antigens related to i) hematopoietic stem and progenitor cells, ii) active cell proliferation, and iii) myeloid cell lineages. Lastly, xenografted zebrafish larvae infected with Klebsiella pneumoniae showed murine immune cells trafficking to bacterial foci and interacting with bacterial cells. Overall, these results show that mammalian bone marrow cells xenografted in zebrafish integrate into the host hematopoietic system revealing highly conserved molecular mechanisms of hematopoiesis between zebrafish and mammals. In addition, this procedure introduces a useful and simple method that improves and broadens the scope of hematopoietic tissue xenotransplantation studies in zebrafish.

developmental biology↗