Runx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo.

Hematopoietic stem cells (HSCs) produce all essential cellular components of the blood. Stromal cell lines supporting HSCs follow a vascular smooth muscle cell (vSMC) differentiation pathway, suggesting that some hematopoiesis-supporting cells originate from vSMC precursors. These pericyte-like precursors were recently identified in the aorta-gonad-mesonephros (AGM) region; however, their role in the hematopoietic development in vivo remains unknown. Here, we identify a subpopulation of NG2+Runx1+ perivascular cells that display a sclerotome-derived vSMC transcriptomic profile. We show that deleting Runx1 in NG2+ cells impairs the hematopoietic development in vivo and causes transcriptional changes in pericytes/vSMCs, endothelial cells and hematopoietic cells in the murine AGM. Importantly, this deletion leads also to a significant reduction of HSC reconstitution potential in the bone marrow in vivo. This defect is developmental, as NG2+Runx1+ cells were not detected in the adult bone marrow, demonstrating the existence of a specialised pericyte population in the HSC-generating niche, unique to the embryo.

Determinación del polimorfismo C677T de metilentetrahidrofolato reductasa (MTHFR) en una población piloto de estudiantes de la Universidad del Rosario / Preliminary population study of Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphism determination in a pilot group of students from the University of Rosario

Introducción: la 5, 10-metilentetrahidrofolato reductasa (MTHFR) es una enzima clave en el metabolismo del folato; sus polimorfismos se han asociado al aumento de riesgo de padecer enfermedad coronaria, problemas obstétricos en mujeres gestantes, desarrollo de fetos con defectos de cierre del tubo neural y susceptibilidad a algunos tipos de cáncer. Este gen presenta una variación polimórfica de nucleótido único, que consiste en un cambio de C por T en la posición 677 el cual afecta de manera notable su actividad enzimática. Objetivo: Dada la importancia de esta enzima y la heterogeneidad genética de la población colombiana se realizó un estudio para determinar las frecuencias alélicas y genotípicas del polimorfismo C677T de MTHFR en individuos sanos, debido a que en el país sólo se han realizado estudios que involucran metodología de casos y controles. Materiales y métodos: Este polimorfismo se estudió a partir de ADN de una muestra poblacional de 206 estudiantes. Adicionalmente, se calcularon las frecuencias globales de Colombia utilizando los datos de controles sanos reportados en otros estudios. Resultados: En la muestra evaluada se detectó un desequilibrio Hardy-Weinberg, mientras que en los datos globales colombianos se encontró que la población está en equilibrio. Conclusión: la frecuencia poblacional del alelo T parece estar sometida a una presión de selección positiva, dado su incremento en la población a pesar de su efecto deletéreo. Un estudio español reporta resultados similares y argumenta como causa probable de este cambio en la frecuencia alélica de T la suplementación con ácido fólico a futuras madres.

Introduction: the 5, 10-methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in folate metabolism; their polymorphisms have been associated with heart disease risk increase, obstetric problems, neural tube defects in fetuses and cancer susceptibility. This gene has a single nucleotide polymorphism, a C-T change at nucleotide 677, which affects significantly its enzymatic activity. Objective: because of the biological importance of this enzyme and the Colombian population genetic heterogeneity characteristic, a study was performed to determine allele and genotype frequencies of MTHFR C677T polymorphism in healthy individuals, taking into account that in Colombia there are only studies that have involved case-control methodology. Methods: we analyzed this polymorphism trough the amplification of the DNA of a 206 students sample population. Additionally, Colombian overall frequencies were calculated, using data from healthy controls reported in other studies. Results: a Hardy-Weinberg disequilibrium was found in the sample tested. For the Colombian data, we found that the global population was in equilibrium. Conclusion: T allele population frequency seems to be under positive selection pressure, which is reflected in the population allele increase, despite its deleterious effect. A Spanish study reported similar results and identified folic acid supplementation on expectant mothers as a probably cause of this change.