16 August 2001. In the August 16 Nature, scientists in the laboratory of Perry
Bartlett, at the Walter and Eliza Hall Institute of Medical Research, Victoria,
Australia, report the successful isolation of multipotent stem cells from adult
mice. The researchers, using fluorescence-activated cell sorting, sifted through
single-cell suspensions of tissue from brain lateral ventricles. They found the
greatest numbers of neuronal stem cells (NSC) in subpopulations that were large
(>12 mm), had low affinity for peanut agglutinin (PNA), and expressed poorly the
ependymal marker, heat-stable antigen (HSA).
80 percent of these NSCs, representing about 0.27 percent of the total cells sorted, were
capable of forming neurospheres. All the neurospheres tested expressed the putative
NSC marker nestin and were able to differentiate to express markers of astrocytes
(glial fibrillary acid protein, GFAP), neurons (bIII tubulin), and oligodendrocytes
(O4). Furthermore, when incubated with myogenic cells these precursors differentiated
into myocyte-like cells expressing the myogenic markers α-actinin-2, and myosin
heavy chain (MyHC).
While recent publications have touted either the ependyma (Johansson
et al.), or the subventricular zone (Doetsch
et al., Chiasson
et al.), as the breeding ground for neuronal stem cells, the present work
suggests that both these layers may contribute to the pool; after labeling the
ependyma with DiI only about 30 percent of the NSCs recovered were DiI positive. Furthermore,
the cells were negative for GFAP, indicating a nonastrocyte origin. "This is
a very elegant series of experiments," said Jeffrey Macklis,
at Harvard Medical School. "It goes a long way toward resolving two outstanding
issues: the precise location and the identity of some of the neuronal precursor
cells in the adult mammalian brain. However, the level of differentiation and
the complexity of the neurons produced have yet to be investigated in detail."
Meanwhile, researchers in Freda Miller's lab at the Montreal Neurological
Institute, McGill University, Canada, report in September's Nature Cell Biology
the successful isolation of stem cells from the dermis of juvenile and adult mice.
These cells were isolated by repeatedly passing cell suspensions through uncoated
culture flasks. This selective adhesion method yielded floating spheres, which
then yielded single cells, dubbed skin-derived precursors (SKPs), with neural
stem cell characteristics.
These SKPs differentiated to express nestin and bIII tubulin. Some could be
coaxed to express other neuron-specific markers including neurofilament-M, enolase,
and glutamic acid decarboxylase, a marker for CNS GABAergic neurons.
Subpopulations of differentiated cells expressed glial cell markers, including
cyclic nucleotide phosphatase, A2B5, and GFAP. These markers occurred in combinations,
either with or without coexpression of nestin, that indicated the presence
of astrocytes, oligodendrocytes, and Schwann cells. SKPs incubated with rat
serum differentiated into mesodermal cell types, including those with smooth
muscle or adipocyte morphology, the former also expressed smooth muscle cell
"This work provides some very convincing evidence for trans-differentiation,"
said Macklis, "but the level of this potential is still unclear. Important yardsticks
for such cells in future analyses will be their level of precision in neuronal
differentiation and their degree of multipotentiality in vivo."-Tom Fagan.
Reference:Rietze RL, Valcanis H, Brooker GF, Thomas T, Voss AK, Bartlett PF. Purification of a pluripotent neural stem cell from the adult mouse brain. Nature. 2001 Aug 16;412(6848):736-9. Abstract
Toma JG, Akhavan M, Fernandes KJ, Barnabe-Heider F, Sadikot A, Kaplan DR, Miller FD. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol. 2001 Sep;3(9):778-84. Abstract