RESUMO
It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of carbon-14, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 25 to 0.45% at the age of 75. Fewer than 50% of cardiomyocytes are exchanged during a normal life span. The capacity to generate cardiomyocytes in the adult human heart suggests that it may be rational to work toward the development of therapeutic strategies aimed at stimulating this process in cardiac pathologies.
Assuntos
DNA/biossíntese , Miócitos Cardíacos/citologia , Adulto , Idoso , Envelhecimento , Radioisótopos de Carbono/análise , Contagem de Células , Núcleo Celular/química , Divisão do Núcleo Celular , Proliferação de Células , Separação Celular , Ecocardiografia Doppler em Cores , Humanos , Pessoa de Meia-Idade , Modelos Cardiovasculares , Miócitos Cardíacos/metabolismo , Armas Nucleares , Poliploidia , Datação Radiométrica , Células-Tronco/citologia , Troponina I/análise , Troponina T/análiseRESUMO
The potential of embryonic stem cells to differentiate to all cell types makes them an attractive model for development and a potential source of cells for transplantation therapies. Candidate approaches have identified individual genes and proteins that promote the differentiation of embryonic stem cells to desired fates. Here, we describe a rapid large-scale screening strategy for the identification of genes that influence the pluripotency and differentiation of embryonic stem cells to specific fates, and we use this approach to identify genes that induce neuron formation. The power of the strategy is validated by the fact that, of the 15 genes that resulted in the largest increase in neuron number, 8 have previously been implicated in neuronal differentiation or survival, whereas 7 represent novel genes or known genes not previously implicated in neuronal development. This is a simple, fast, and generally applicable strategy for the identification of genes promoting the formation of any specific cell type from embryonic stem cells. Disclosure of potential conflicts of interest is found at the end of this article.