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1.
Dev Cell ; 58(24): 2881-2895.e7, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-37967560

RESUMEN

Generating organs from stem cells through blastocyst complementation is a promising approach to meet the clinical need for transplants. In order to generate rejection-free organs, complementation of both parenchymal and vascular cells must be achieved, as endothelial cells play a key role in graft rejection. Here, we used a lineage-specific cell ablation system to produce mouse embryos unable to form both the cardiac and vascular systems. By mouse intraspecies blastocyst complementation, we rescued heart and vascular system development separately and in combination, obtaining complemented hearts with cardiomyocytes and endothelial cells of exogenous origin. Complemented chimeras were viable and reached adult stage, showing normal cardiac function and no signs of histopathological defects in the heart. Furthermore, we implemented the cell ablation system for rat-to-mouse blastocyst complementation, obtaining xenogeneic hearts whose cardiomyocytes were completely of rat origin. These results represent an advance in the experimentation towards the in vivo generation of transplantable organs.


Asunto(s)
Sistema Cardiovascular , Corazón , Células Madre Pluripotentes , Animales , Ratones , Ratas , Blastocisto , Células Endoteliales , Miocitos Cardíacos , Corazón/embriología , Sistema Cardiovascular/embriología
2.
Stem Cell Reports ; 18(1): 64-80, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36563688

RESUMEN

Naive human pluripotent stem cells (hPSCs) are defined as the in vitro counterpart of the human preimplantation embryo's epiblast and are used as a model system to study developmental processes. In this study, we report the discovery and characterization of distinct cell populations coexisting with epiblast-like cells in 5iLAF naive human induced PSC (hiPSC) cultures. It is noteworthy that these populations closely resemble different cell types of the human embryo at early developmental stages. While epiblast-like cells represent the main cell population, interestingly we detect a cell population with gene and transposable element expression profile closely resembling the totipotent eight-cell (8C)-stage human embryo, and three cell populations analogous to trophectoderm cells at different stages of their maturation process: transition, early, and mature stages. Moreover, we reveal the presence of cells resembling primitive endoderm. Thus, 5iLAF naive hiPSC cultures provide an excellent opportunity to model the earliest events of human embryogenesis, from the 8C stage to the peri-implantation period.


Asunto(s)
Embrión de Mamíferos , Células Madre Pluripotentes , Humanos , Desarrollo Embrionario/genética , Endodermo , Estratos Germinativos , Diferenciación Celular/genética , Blastocisto
3.
Glob Chang Biol ; 23(3): 1258-1281, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27387228

RESUMEN

A potato crop multimodel assessment was conducted to quantify variation among models and evaluate responses to climate change. Nine modeling groups simulated agronomic and climatic responses at low-input (Chinoli, Bolivia and Gisozi, Burundi)- and high-input (Jyndevad, Denmark and Washington, United States) management sites. Two calibration stages were explored, partial (P1), where experimental dry matter data were not provided, and full (P2). The median model ensemble response outperformed any single model in terms of replicating observed yield across all locations. Uncertainty in simulated yield decreased from 38% to 20% between P1 and P2. Model uncertainty increased with interannual variability, and predictions for all agronomic variables were significantly different from one model to another (P < 0.001). Uncertainty averaged 15% higher for low- vs. high-input sites, with larger differences observed for evapotranspiration (ET), nitrogen uptake, and water use efficiency as compared to dry matter. A minimum of five partial, or three full, calibrated models was required for an ensemble approach to keep variability below that of common field variation. Model variation was not influenced by change in carbon dioxide (C), but increased as much as 41% and 23% for yield and ET, respectively, as temperature (T) or rainfall (W) moved away from historical levels. Increases in T accounted for the highest amount of uncertainty, suggesting that methods and parameters for T sensitivity represent a considerable unknown among models. Using median model ensemble values, yield increased on average 6% per 100-ppm C, declined 4.6% per °C, and declined 2% for every 10% decrease in rainfall (for nonirrigated sites). Differences in predictions due to model representation of light utilization were significant (P < 0.01). These are the first reported results quantifying uncertainty for tuber/root crops and suggest modeling assessments of climate change impact on potato may be improved using an ensemble approach.


Asunto(s)
Cambio Climático , Solanum tuberosum , Biomasa , Bolivia , Dinamarca , Modelos Teóricos , Washingtón
4.
Funct Integr Genomics ; 11(2): 275-91, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21274588

RESUMEN

In potatoes and many other crops, drought is one of the most important environmental constraints leading to yield loss. Development of drought-tolerant cultivars is therefore required for maintaining yields under climate change conditions and for the extension of agriculture to sub-optimal cropping areas. Drought tolerance mechanisms have been well described for many crop plants including Native Andean potato. However, knowledge on tolerance traits suitable for commercial potato varieties is scarce. In order to describe drought tolerance mechanisms that sustain potato yield under water stress, we have designed a growth-chamber experiment with two Solanum tuberosum L. cultivars, the more drought tolerant accession 397077.16, and the sensitive variety Canchan. After 21 days of drought exposure, gene expression was studied in leaves using cDNA microarrays. The results showed that the tolerant clone presented more differentially expressed genes than the sensitive one, suggesting greater stress response and adaptation. Moreover, it exhibited a large pool of upregulated genes belonging to cell rescue and detoxication such as LEAs, dehydrins, HSPs, and metallothioneins. Transcription factors related to abiotic stresses and genes belonging to raffinose family oligosaccharide synthesis, involved in desiccation tolerance, were upregulated to a greater extent in the tolerant clone. This latter result was corroborated by biochemical analyses performed at 32 and 49 days after drought that showed an increase in galactinol and raffinose especially in clone 397077.16. The results depict key components for the drought tolerance of this advanced potato clone.


Asunto(s)
Metabolismo de los Hidratos de Carbono/genética , Sequías , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Células Clonales , Exposición a Riesgos Ambientales , Perfilación de la Expresión Génica , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas de Plantas/genética , Rafinosa/genética , Rafinosa/metabolismo , Selección Genética
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