Finding the path to a source of stem cells

The first wave of cells giving rise to an early stem cell population are derived from cells of the neural tube

Researchers from Japan and the UK have identified a source of cells that give rise to mesenchymal stem cells (MSCs)—a population of stem cells that can develop into various mature cell types, including bone, cartilage and fat cells.

MSCs have received much attention recently due to their pluripotency, or ability to generate numerous cell types, their ready availability from adult animals, including humans, and their successful use for stem cell therapy in the clinic. Although thought to originate from either the mesoderm or neural crest of the embryo, the exact origins and endogenous function of these cells in the body have eluded scientists.

Now, Takumi Era, Shin-Ichi Nishikawa at the RIKEN Center for Developmental Biology, Kobe, and colleagues have identified the initial source of these cells as the neuroepithelium—the sheet of cells derived from neural crest cells that contain sensory neurons—along the body’s trunk (1).

Initially working in vitro, the team used a mouse embryonic stem cell line to show that cells that start out expressing Sox1, a genetic marker of neuroepithelial cells, end up expressing PDGFRα, a marker of MSCs, before the cells eventually differentiate into fat cells. The researchers then genetically marked the Sox1+ cells of the mouse trunk (Fig. 1), mechanically isolated all the cells from this location of the body and showed that only the Sox1+ cells could behave like valid MSCs in culture, indicating that MSCs start out as neuroepithelial cells and not other cell types.

To then show that this differentiation pathway also occurs in vivo, the team performed lineage analyses by using a Sox1+-marked mouse strain and following the fate of these cells as the embryo developed. The team found that the marked cells in the body also switched to expressing PDGFRα after a few days, indicating their conversion from neuroepithelial cells to MSCs. However by the neonatal stage, the number of marked MSCs was reduced significantly by the time they had migrated to the bone marrow, indicating that these MSCs are derived from a transient wave of differentiation.

Given that the researchers detected many more unmarked MSCs in the bone marrow, they intend to explore whether other sources of MSCs may occur later in embryonic development, independent of the neuroepithelium.

Era and Nishikawa feel that, in addition to identifying the initial source of MSCs in utero, they have developed methods to enrich MSC progenitors and to identify the cell lineage of additional cell types that could give rise to other types of adult stem cells.


1. Takashima, Y., Era, T., Nakao, K., Kondo, S., Kasuga, M., Smith, A.G. & Nishikawa, S. Neuroepithelial cells supply an initial transient wave of MSC differentiation. Cell 129, 1377–1388 (2007).

Published: 07 Dec 2007


Contact details:

2-1, Hirosawa, Wako, 351-0198

News topics: 
Content type: 
Websites: Figure 1: A mouse embryo used to show that Sox1+ cells of the trunk can give rise to MSCs in culture.