Human stromal stem cell populations reside in different tissues and anatomical sites, however a critical question related to their efficient use in regenerative medicine is whether they exhibit equivalent biological properties. Here, we compared cellular and molecular characteristics of stromal stem cells derived from the bone marrow, at different body sites (iliac crest, sternum, and vertebrae) and other tissues (dental pulp and colon). In particular, we investigated whether homeobox genes of the HOX and TALE subfamilies might provide suitable markers to identify distinct stromal cell populations, as HOX proteins control cell positional identity and, together with their co-factors TALE, are involved in orchestrating differentiation of adult tissues. Our results show that stromal populations from different sources, although immunophenotypically similar, display distinct HOX and TALE signatures, as well as different growth and differentiation abilities. Stromal stem cells from different tissues are characterized by specific HOX profiles, differing in the number and type of active genes, as well as in their level of expression. Conversely, bone marrow-derived cell populations can be essentially distinguished for the expression levels of specific HOX members, strongly suggesting that quantitative differences in HOX activity may be crucial. Taken together, our data indicate that the HOX and TALE profiles provide positional, embryological and hierarchical identity of human stromal stem cells. Furthermore, our data suggest that cell populations derived from different body sites may not represent equivalent cell sources for cell-based therapeutical strategies for regeneration and repair of specific tissues.

Retinal homeobox (Rx) genes, with representatives in vertebrates and invertebrates, encode fundamental regulators of early eye and brain formation. Here we describe the spatiotemporal expression profile of a candidate planarian orthologue of Rx during regeneration in Dugesia japonica and Schmidtea mediterranea. Although low levels of Rx transcripts were found throughout the body of intact planarians, high levels of Rx expression were specific to regenerating tissue in both head and tail fragments. We also observed that Rx was never expressed in the simple rhabdomeric planarian eyes, supporting the notion that only formation of eyes that use the ciliary type of photoreceptors requires Rx function. KEY WORDS: paired-class homeobox gene, Rx, planarian, regeneration, eyeRx paired-type homeobox transcription factors have been isolated in several vertebrate and invertebrate species (Arendt et al., 2004; Bailey et al., 2004 and references therein;D'Aniello et al., 2006). A growing body of evidence suggests that Rx genes, early expressed in the anterior neural plate, are essential for the proliferation and specification of retina progenitor cells in chordates. In invertebrates, such as Drosophila, Rx does not seem to play a similar role. In fact, Drosophila Rx is not required for the formation of the visual system, but only for brain and clypeus development (Davis et al., 2003). In addition, an Rx ortholog of the annelid Platynereis has been found expressed in the ciliary photoreceptor cells of the brain, but not in the rhabdomeric photoreceptors of the larval and differentiating adult eyes (Arendt et al., 2004). Based on these observations, it has been proposed that an Rx ancestral function was related to the regulation of genes involved in brain development. During evolution, Rx genes became then essential for development of photoreceptors of ciliary type. No data are available on the function of Rx genes in a context different from the embryonic development, such as regeneration. Planarians (Platyhelminthes, Lophotrochozoa) offer a suitable model to investigate the role of Rx during regeneration. These organisms indeed can regenerate heads, including a complete brain, as well as other body parts in a short time, by virtue of the activity of adult stem cells, called neoblasts Saló 2006;Sánchez Alvarado, 2006). Planarian brain consists of two anterior cephalic ganglia connected to two ventral Int. J. Dev. Biol. 52: 1113-1117 (2008) nerve cords that run along the body (Cebrià, 2007). A pair of simple rhabdomeric eyes is generally located on its dorsal side. Despite the planarian central nervous system (CNS) seems quite simple at the morphological level, it possesses a functionally and molecularly complex structure (Cebrià, 2007 and references therein).We have cloned and sequenced the cDNA of a planarian Rx homolog in Dugesia japonica (GI strain) and Schmidtea mediterranea (asexual strain). Animals were maintained in autoclaved stream water at 18°C and starved for two weeks before being used in the experimen...