Deconstructing the complexity of a microenvironmental niche

Abstract

Cells acquire their fate in vivo in the context of a complex microenvironmental "niche" comprised of heterologous cell types, signaling molecules, extracellular matrix, biophysical forces, and metabolic substrates. Now Calderón and Boehm report the "refunctionalization" of a defective thymic epithelial niche, offering insights into how signaling molecules may be hierarchically organized to direct differentiation outcomes.

Figure 1. Recipe for Refunctionalizing a Thymic Niche

(A) Simplified schema of a normal thymus in a mouse expressing the transcription factor Foxn1. (B) The same schema for a thymus of a nude mouse that does not express Foxn1; here the thymus lacks hematopoietic elements. (C–F) By re-expressing individual signaling factors in the thymus of the nude mice—Ccl25 (C), Scf (D), Cxcl12 (E), and DLL4 (F)—Calderón and Boehm (2012) uncover a hierarchical restructuring of the thymus. The combined expression of factors leads to phenotypes as described in this Preview.