Adipose Rex

Abstract

Traditionally, it has been considered the province of proteins to regulate cell lineage determination in both embryonic and adult cellular differentiation. Homeodomain proteins, the products of homeobox genes, are the classic rulers of overall embryonic body patterning with its axial symmetries and asymmetries. These homeodomain transcription factors along with other morphogenetic proteins also influence identity in adult tissues, through downstream targets, some of which remain unknown. In blood and tissue, lineage determination seems to occur through a hierarchical organization. The best-characterized differentiation hierarchy is that of the hematopoietic lineages in bone marrow. Precursors of blood cells are guided to differentiate along sequentially branching myelocytic or erythrocytic lineages by proteins collectively termed the “colony-stimulating factors.” Precursors of connective tissue and other mesenchymal cells also seem to follow a lineage hierarchy, remarkably similar to that of neural crest cells in the embryo.1 Just as hematopoietic precursor cells persist as stem cells in adult marrow, there is now evidence that pluripotent mesenchymal precursor cells, possibly qualifying as “stem” cells, also persist in adult tissues.2–4⇓⇓ Most importantly, these so-called mesenchymal stem cells actively repopulate connective tissue.5 This has important implications for human health, given the potential to harvest and harness these cells for cultivation and replacement at sites of nonhealing injuries.6 Implementation of such a novel potential therapy will require detailed knowledge of the factors that determine commitment to a specific lineage. Some of the regulatory factors orchestrating mesenchymal differentiation have been identified, but many remain unknown. A particularly interesting aspect of the mesenchymal differentiation hierarchy is that it seems to be regulated not only by protein factors but also by lipids and …