Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis.
Bone marrow stromal stem cells (MSCs) normally differentiate into mesenchymal derivatives but recently have also been converted into neurons, classical ectodermal cells. To begin defining underlying mechanisms, we extended our characterization of MSCs and the differentiated neurons. In addition to expected mesodermal mRNAs, populations and clonal lines of MSCs expressed germinal, endodermal, and ectodermal genes. Thus, the MSCs are apparently "multidifferentiated" in addition to being multipotent. Conversely, the differentiating neurons derived from populations and clonal lines of MSCs expressed the specific markers beta-III tubulin, tau, neurofilament-M, TOAD-64, and synaptophysin de novo. The transmitter enzymes tyrosine hydroxylase and choline acetyltransferase were localized to neuronal subpopulations. Our observations suggest that MSCs are already multidifferentiated and that neural differentiation comprises quantitative modulation of gene expression rather than simple on-off switching of neural-specific genes.
Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. woodburydl@aol.com
Dale
D
Woodbury
Kathleen
K
Reynolds
Ira B
IB
Black
D000367:Age Factors; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002999:Clone Cells; D004475:Ectoderm / Q000166:cytology; D004707:Endoderm / Q000166:cytology; D005269:Femur / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D051381:Rats; D017154:Stromal Cells / Q000166:cytology* / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics
D009419:Nerve Tissue Proteins