Miguel Martin

Publications (5)20.2 Total impact

• Source

  Available from: Francisco J Iborra

  Article: Cord blood-derived CD34+ hematopoietic cells with low levels of mitochondrial mass are enriched in hematopoietic repopulating stem cell function.

  Damia Romero-Moya, Clara Bueno, Rosa Montes, Oscar Navarro-Montero, Francisco J Iborra, Luis Carlos López, Miguel Martin, Pablo Menendez
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND. The homeostasis of the hematopoietic stem/progenitor cell pool relies on a fine-tuned balance between self-renewal, differentiation and proliferation. Recent studies have proposed that mitochondria regulate these processes. Although recent work has contributed to understand the role of mitochondria during stem cell differentiation, it remains elusive whether the mitochondrial content/function impacts human hematopoietic stem versus progenitor function. DESIGN AND METHODS. We report that mitochondrial mass highly correlates with mitochondrial membrane potential in CD34+ hematopoietic stem/progenitor cells. Therefore, cord blood CD34+ cells were sorted based on their mitochondrial mass, and the in vitro homeostasis and clonogenic potential as well as the in vivo repopulating potential of CD34+ cells with high (CD34+ MitoHigh) versus low (CD34+ MitoLow) mitochondrial mass was analyzed. RESULTS. CD34+ MitoLow fraction contains 6-fold higher numbers of CD34+CD38- primitive cells, and is enriched in hematopoietic stem cell function as demonstrated by its significantly higher hematopoietic reconstitution potential in immunedeficient mice. In contrast, the CD34+ MitoHigh fraction is more enriched in hematopoietic progenitor function with higher in vitro clonogenic capacity. In vitro differentiation of CD34+ MitoLow cells is significantly delayed as compared to CD34+ MitoHigh cells. The eventual complete differentiation of CD34+ MitoLow cells, which coincides with a robust expansion of the CD34- differentiated progeny, is accompanied by a mitochondrial adaptation as shown by a significant increase in ATP production and expression of the mitochondrial genes ND1 and COX2. CONCLUSIONS. Cord blood CD34+ cells with low levels of mitochondrial mass are enriched in hematopoietic repopulating stem cell function whereas high levels of mitochondrial mass identify hematopoietic progenitors. A mitochondrial response underlies hematopoietic stem/progenitor cell differentiation and proliferation of lineage-committed CD34- cells.
  Haematologica 01/2013; · 6.42 Impact Factor
• Source

  Available from: Fernando Cardona

  Dataset: journalnutrition2008

  Rosa Bernal, Fernando Cardona, Miguel Martin, Manuel Macias-Gonzalez, Francisco J Tinahones, Maribel Queipo-Ortuño
• Article: Obesity short-circuits stemness gene network in human adipose multipotent stem cells.

  Mar Roldan, Manuel Macias-Gonzalez, Regina Garcia, Francisco J Tinahones, Miguel Martin
  [show abstract] [hide abstract]
  ABSTRACT: The discovery of adipose multipotent stem cells has provided new insights to explore cellular mechanisms involved in adipose tissue function. In the present work, we aimed to evaluate how the adipogenic environment influences the stemness of the resident multipotent stem cells. To achieve this goal, human omental multipotent stem cells (hO-MSCs) were isolated, expanded, and characterized in both healthy lean and morbidly obese individuals. We observed decreased cell proliferation, premature senescence, and increased cytokine secretion associated with increasing body mass index of the patients. Consistent with the latter finding, the hO-MSCs derived from patients with morbid obesity lose their multilineage differentiation capacity associated with a dysregulation in the Wnt, Notch, and Sonic Hedgehog signaling pathways. Moreover, microRNAs involved in the regulation of stemness, cell differentiation, and senescence were also up-regulated in obese individuals. Altogether, our data show that obesity causes a general short circuit in the stemness gene network of hO-MSCs.
  The FASEB Journal 08/2011; 25(12):4111-26. · 5.71 Impact Factor
• Article: The adaptation of human embryonic stem cells to different feeder-free culture conditions is accompanied by a mitochondrial response.

  Verónica Ramos-Mejia, Clara Bueno, Mar Roldan, Laura Sanchez, Gertrudis Ligero, Pablo Menendez, Miguel Martin
  [show abstract] [hide abstract]
  ABSTRACT: The mitochondrial contribution to the maintenance of human embryonic stem cell (hESC) pluripotency and culture homeostasis remains poorly understood. Here, we sought to determine whether hESC adaptation to different feeder-free culture conditions is linked to a mitochondrial adaptation. The expression of ESC pluripotency factors and parameters of mitochondrial contribution including mitochondrial membrane potential, mtDNA content, and the expression of master mitochondrial genes implicated in replication, transcription, and biogenesis were determined in 8 hESC lines maintained in 2 distinct human feeders-conditioned media (CM): human foreskin fibroblast-CM (HFF-CM) and mesenchymal stem cell-CM (MSC-CM). We show a robust parallel trend between the expression of ESC pluripotency factors and the mitochondrial contribution depending on the culture conditions employed to maintain the hESCs, with those in MSC-CM consistently displaying increased levels of pluripotency markers associated to an enhanced mitochondrial contribution. The differences in the mitochondrial status between hESCs maintained in MSC-CM versus HFF-CM respond to coordinated changes in mitochondrial gene expression and biogenesis. Importantly, the culture conditions determine the mitochondrial distribution within the stage-specific embryonic antigen 3 positive (SSEA3(+)) and negative (SSEA3(-)) isolated cell subsets. hESC colonies in MSC-CM display an "intrinsic" high mitochondrial status which may suffice to support undifferentiated growth, whereas hESC colonies maintained in HFF-CM show low mitochondrial status, possibly relying on the production of autologous niche with higher mitochondrial status to support pluripotency and culture homeostasis. Pluripotency markers and mitochondrial status are concomitantly reverted on changing the culture conditions, supporting an unrecognized role of the mitochondria in response to hESC culture adaptation. We provide the first evidence supporting that hESCs adaptation to different feeder-free culture systems relies on a mitochondrial response.
  Stem cells and development 06/2011; 21(7):1145-55. · 4.15 Impact Factor
• Article: PPARgamma mRNA expression is reduced in peripheral blood mononuclear cells after fat overload in patients with metabolic syndrome.

  Manuel Macias-Gonzalez, Fernando Cardona, Maribel Queipo-Ortuño, Rosa Bernal, Miguel Martin, Francisco J Tinahones
  [show abstract] [hide abstract]
  ABSTRACT: PPARgamma is a transcriptional regulator of metabolism; its activity can be modulated by direct binding of dietary lipids. The most prevalent human PPARgamma gene variant, Ala12, is associated with postprandial hypertriglyceridemia in patients with metabolic syndrome, although the mechanism whereby this polymorphism affects lipid homeostasis remains to be fully determined. Using peripheral blood mononuclear cells (PBMC), we studied the effect of the Pro12 and Ala12 polymorphisms on mRNA expression of PPARgamma and nuclear factor kappa B genes before and 3 and 4 h after fat overload. We also studied several biochemical and oxidative stress variables. Most of the indicators of oxidative stress were higher in patients with metabolic syndrome than in healthy subjects before and after fat overload. Patients also differed depending on whether they had the Pro12 or Ala12 variant in PBMC; PPARgamma expression was lower in healthy subjects compared with patients. After fat overload, circulating triglycerides and PPARgamma expression were positively correlated (r = 0.617, P < 0.05), and PPARgamma expression tended to be negatively correlated with 2 important markers of oxidative stress: plasma lipid peroxidation (r = -0.224, P < 0.1) and carbonylated proteins (CPro) (r = -0.340, P < 0.1) concentrations. We also found differences in several indicators of oxidative stress between Pro12 and Ala12 patients, including an increase in plasma CPro before and after fat overload in Ala12 but not Pro12 patients. These data provide evidence that the Ala12 sequence variant is associated with a worse metabolic profile than Pro12. This is related to differences in the expression of PPARgamma and to oxidative imbalance after fat overload.
  Journal of Nutrition 05/2008; 138(5):903-7. · 3.92 Impact Factor