RESUMO
We describe here the isolation of stem cells from juvenile and adult rodent skin. These cells derive from the dermis, and clones of individual cells can proliferate and differentiate in culture to produce neurons, glia, smooth muscle cells and adipocytes. Similar precursors that produce neuron-specific proteins upon differentiation can be isolated from adult human scalp. Because these cells (termed SKPs for skin-derived precursors) generate both neural and mesodermal progeny, we propose that they represent a novel multipotent adult stem cell and suggest that skin may provide an accessible, autologous source of stem cells for transplantation.
Assuntos
Diferenciação Celular/fisiologia , Sistema Nervoso/citologia , Pele/citologia , Células-Tronco/citologia , Células-Tronco/fisiologia , Adipócitos/citologia , Envelhecimento , Animais , Animais Recém-Nascidos , Técnicas de Cultura de Células , Divisão Celular , Células Clonais , Humanos , Camundongos , Camundongos Transgênicos , Músculo Liso/citologia , Neuroglia/citologia , Neurônios/citologia , Regiões Promotoras Genéticas , Pele/crescimento & desenvolvimento , Tubulina (Proteína)/genética , beta-Galactosidase/análise , beta-Galactosidase/genéticaRESUMO
The retinoblastoma tumor suppressor protein (pRb) family is essential for cortical progenitors to exit the cell cycle and survive. In this report, we test the hypothesis that pRb collaborates with basic helix-loop-helix (bHLH) transcription factors to regulate cortical neurogenesis, taking advantage of the naturally occurring dominant-inhibitory HLH protein Id2. Overexpression of Id2 in cortical progenitors completely inhibited the induction of neuron-specific genes and led to apoptosis, presumably as a consequence of conflicting differentiation signals. Both of these phenotypes were rescued by coexpression of a constitutively activated pRb mutant. In contrast, Id2 overexpression in postmitotic cortical neurons affected neither neuronal gene expression nor survival. Thus, pRb collaborates with HLHs to ensure the coordinate induction of terminal mitosis and neuronal gene expression as cortical progenitors become neurons.