Skin cells called fibroblasts can be transformed into neurons quickly and efficiently with just a few genetic tweaks, according to new research. The surprisingly simple conversion, which doesn’t require the cells to be returned to an embryonic state, suggests that differentiated adult cells are much more flexible than previously thought.
If the research, published in the journal Nature yesterday, can be repeated in human cells, it would provide an easier method for generating replacement neurons from individual patients. Brain cells derived from a skin graft would be genetically identical to the patient and therefore remove the risk of immune rejection–such an approach might one day be used to treat Parkinson’s or other neurodegenerative diseases.
“It’s almost scary to see how flexible these cell fates are,” says Marius Wernig, a biologist at the Institute for Stem Cell Biology and Regenerative Medicine at Stanford, who led the research. “You just need a few factors, and within four to five days you see signs of neuronal properties in these cells.”
Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Generation of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine.
Physorg report – Using cells from mice, scientists from Iowa and Iran have discovered a new strategy for making embryonic stem cell transplants less likely to be rejected by a recipient’s immune system. This strategy, described in a new research report appearing in the February 2010 print issue of The FASEB Journal, involves fusing bone marrow cells to embryonic stem cells. Once fused, the hybrid cells have DNA from both the donor and recipient, raising hopes that immune rejection of embryonic stem cell therapies can be avoided without drugs.
Bone marrow transplantation is a curative treatment for many diseases, including leukemia, autoimmune diseases, and a number of immunodeficiencies. Recently, it was claimed that bone marrow cells transdifferentiate, a much desired property as bone marrow cells are abundant and therefore could be used in regenerative medicine to treat incurable chronic diseases. Using a Cre/loxP system, we studied cell fusion after bone marrow transplantation. Fused cells were chiefly Gr-1+, a myeloid cell marker, and found predominantly in the bone marrow; in parenchymal tissues. Surprisingly, fused cells were most abundant in the kidney, Peyer’s patches, and cardiac tissue. In contrast, after cell fusion with embryonic stem cells, bone marrow cells were reprogrammed into new tetraploid pluripotent stem cells that successfully differentiated into beating cardiomyocytes. Together, these data suggest that cell fusion is ubiquitous after cellular transplants and that the subsequent sharing of genetic material between the fusion partners affects cellular survival and function. Fusion between tumor cells and bone marrow cells could have consequences for tumor malignancy.—Bonde, S., Pedram, M., Stultz, R., Zavazava, N. Cell fusion of bone marrow cells and somatic cell reprogramming by embryonic stem cells.
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