Given our recent finding that the lymph node (LN) can serve as an in vivo factory to generate complex structures like liver, pancreas, and thymus, we investigated whether LN could also support early development and maturation from several mid-embryonic (E14.5/15.5) mouse tissues including brain, thymus, lung, stomach, and intestine. Here we observed brain maturation in LN by showing the emergence of astrocytes with well-developed branching processes. Thymus maturation in LN was monitored by changes in host immune cells. Finally, newly terminally differentiated mucus-producing cells were identified in ectopic tissues generated by transplantation of lung, stomach and intestine in LN. Thus, we speculate the LN offers a unique approach to study the intrinsic and extrinsic differentiation potential of cells and tissues during early development, and provides a new site for bioengineering complex body parts.
Keywords: 21wEcT, 21-week ectopic thymus; 2D, 2-dimensional; 3D, 3-dimensional; 3wEcI, 3-week ectopic intestine; 3wEcL, 3-week ectopic lung; 3wEcS, 3-week ectopic stomach; 6wEcT, 6-week ectopic thymus; AdT, adult thymus; Aire, autoimmune regulator; CgA, chromogranin A; E14.5/15.5, embryonic day 14.5 to 15.5; ECM, extracellular matrix; ER-TR7, reticular fibroblasts and reticular fibers; EmI, embryonic intestine; EmL, embryonic lung; EmS, embryonic stomach; EmT, embryonic thymus; EpCAM1, epithelial cell adhesion molecule 1; FACS, fluorescence-activated cell sorting; FAH, fumarylacetoacetate hydrolase; GFAPδ, glial fibrillary acid protein delta; GM-CSF, granulocyte-macrophage colony-stimulating factor; K5, keratin 5; K8, keratin 8; LN, lymph node; MAP-2, Microtubule-associated protein 2; bioreactor; cTEC, cortical thymic epithelial cell; chimerism; development; lymph node; mTEC, medullary thymic epithelial cell; mTOR, mammalian target of rapamycin; terminal differentiation.