Cloned myogenic cells can transdifferentiate in vivo into neuron-like cells

• Published in: PloS one Vol. 5; no. 1; p. e8814
• Main Authors: Sarig, Rachel, Fuchs, Ora, Tencer, Lilach, Panski, Avi, Nudel, Uri, Yaffe, David
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21-01-2010; Public Library of Science (PLoS)
• Subjects: Animals; Animals, Newborn; Ataxia; Biology; Biopsy; Brain; Brain - cytology; Brain cancer; Brain research; Cell Biology; Cell culture; Cell Differentiation; Cell Transplantation; Cells (biology); Central nervous system; Clone Cells; Cloning; Deoxyribonucleic acid; Developmental Biology; DNA; Embryos; Flow Cytometry; Hospitals; Humans; Inoculation; Mice; Molecular Biology; Muscles - chemistry; Musculoskeletal system; Neural stem cells; Neurofilaments; Neuronal-glial interactions; Neurons; Neurons - cytology; Proteins; Rodents; Science; Somatic cells; Spinal cord; Stem cells; Stem Cells - cytology; Telomerase; Traumatic brain injury; Tumorigenesis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0008814

The question of whether intact somatic cells committed to a specific differentiation fate, can be reprogrammed in vivo by exposing them to a different host microenvironment is a matter of controversy. Many reports on transdifferentiation could be explained by fusion with host cells or reflect intrinsic heterogeneity of the donor cell population.
We have tested the capacity of cloned populations of mouse and human muscle progenitor cells, committed to the myogenic pathway, to transdifferentiate to neurons, following their inoculation into the developing brain of newborn mice. Both cell types migrated into various brain regions, and a fraction of them gained a neuronal morphology and expressed neuronal or glial markers. Likewise, inoculated cloned human myogenic cells expressed a human specific neurofilament protein. Brain injected donor cells that expressed a YFP transgene controlled by a neuronal specific promoter, were isolated by FACS. The isolated cells had a wild-type diploid DNA content.
These and other results indicate a genuine transdifferentiation phenomenon induced by the host brain microenvironment and not by fusion with host cells. The results may potentially be relevant to the prospect of autologous cell therapy approach for CNS diseases.