In vivo partial cellular reprogramming enhances liver plasticity and regeneration.

Mammals have limited regenerative capacity, whereas some vertebrates, like fish and salamanders, are able to regenerate their organs efficiently. The regeneration in these species depends on cell dedifferentiation followed by proliferation. We generate a mouse model that enables the inducible expression of the four Yamanaka factors (Oct-3/4, Sox2, Klf4, and c-Myc, or 4F) specifically in hepatocytes. Transient in vivo 4F expression induces partial reprogramming of adult hepatocytes to a progenitor state and concomitantly increases cell proliferation. This is indicated by reduced expression of differentiated hepatic-lineage markers, an increase in markers of proliferation and chromatin modifiers, global changes in DNA accessibility, and an acquisition of liver stem and progenitor cell markers. Functionally, short-term expression of 4F enhances liver regenerative capacity through topoisomerase2-mediated partial reprogramming. Our results reveal that liver-specific 4F expression in vivo induces cellular plasticity and counteracts liver failure, suggesting that partial reprogramming may represent an avenue for enhancing tissue regeneration.

In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche.

Short-term, systemic expression of the Yamanaka reprogramming factors (Oct-3/4, Sox2, Klf4 and c-Myc [OSKM]) has been shown to rejuvenate aging cells and promote tissue regeneration in vivo. However, the mechanisms by which OSKM promotes tissue regeneration are unknown. In this work, we focus on a specific tissue and demonstrate that local expression of OSKM, specifically in myofibers, induces the activation of muscle stem cells or satellite cells (SCs), which accelerates muscle regeneration in young mice. In contrast, expressing OSKM directly in SCs does not improve muscle regeneration. Mechanistically, expressing OSKM in myofibers regulates the expression of genes important for the SC microenvironment, including upregulation of p21, which in turn downregulates Wnt4. This is critical because Wnt4 is secreted by myofibers to maintain SC quiescence. Thus, short-term induction of the Yamanaka factors in myofibers may promote tissue regeneration by modifying the stem cell niche.

[Effect of quinua (Chenopodium quinoa)consumption as a coadjuvant in nutritional intervention in prediabetic subjects]. / Efecto del consumo de quinua (Chenopodium quinoa)como coadyuvante en la intervención nutricional en sujetos prediabéticos.

INTRODUCTION: Quinoa is a pseudocereal containing low glycemic index carbohydrates, dietary fiber, high biological value protein, phytosterols, and n-3 and n-6 fatty acids, which has generated interest in prediabetes nutritional interventions. This randomized (2:1), placebo-controlled, double-blind study evaluated the effects of processed quinoa on body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG) and the satiation and fullness (complete) degree in prediabetic patients. MATERIAL AND METHOD: Thirty patients were randomized (2:1) in two study arms: Kuska Active product (processed quinoa) and placebo (maltodextrin), with an intake period of 28 days. BMI, HbA1c and FPG were determined before starting treatment and at 28-day intake. Satiety and fullness sensation were just assessed by visual analog scale (VAS) at the day 28. ANOVA was performed for repeated measures with two factors to study (within-subject factor: time; intersubject factor: product consumed) to demonstrate the effectiveness of processed quinoa on the study variables. RESULTS: Twenty-nine patients (placebo, n = 10; quinoa, n = 19) completed the study, and the quinoa group shows a significant decrease in BMI (p < 0.05) and HbA1c values (p < 0.001), and an increase in the satiation and fullness (complete) degree (p < 0.001). No significant differences were found in FPG levels from baseline to post-intake period. CONCLUSIONS: The results show that processed quinoa intake during 28 days decreases BMI and HbA1c levels, maintains FPG levels, and incr eases the satiation and fullness (complete) degree in prediabetic patients.