16 Aug 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., 1999), or the subventricular zone (Doetsch et al., 1999; Chiasson et al., 1999), 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 actin.

"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

Comments

1. • Benjamin Wolozin
     Boston University School of Medicine
   • Posted: 29 Jun 2002
   • Paper: Purification of a pluripotent neural stem cell from the adult mouse brain.

   "An important reason for using embryonic stem cells for research is that only these cells can generate neuronal stem cells. The finding presented in this paper demonstrates that neuronal stem cells can be generated from adult tissue. This will facilitate research into neuronal stem cells, by circumventing on of the major political controversies raging in our nation. Thus, this finding is very important."

   View all comments by Benjamin Wolozin

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Further Reading

Papers

1. Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisén J. Identification of a neural stem cell in the adult mammalian central nervous system. Cell. 1999 Jan 8;96(1):25-34. PubMed.
2. Doetsch F, Caillé I, Lim DA, García-Verdugo JM, Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell. 1999 Jun 11;97(6):703-16. PubMed.
3. Chiasson BJ, Tropepe V, Morshead CM, van der Kooy D. Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential, but only subependymal cells have neural stem cell characteristics. J Neurosci. 1999 Jun 1;19(11):4462-71. PubMed.