Sox2-Mediated Regulation of Adult Neural Crest Precursors and Skin Repair

Abstract

Nerve-derived neural crest cells are essential for regeneration in certain animals, such as newts. Here, we asked whether they play a similar role during mammalian tissue repair, focusing on Sox2-positive neural crest precursors in skin. In adult skin, Sox2 was expressed in nerve-terminal-associated neural crest precursor cells (NCPCs) around the hair follicle bulge, and following injury was induced in nerve-derived cells, likely dedifferentiated Schwann cell precursors. At later times postinjury, Sox2-positive cells were scattered throughout the regenerating dermis, and lineage tracing showed that these were all neural-crest-derived NCPCs. These Sox2-positive NCPCs were functionally important, since acute deletion of Sox2 prior to injury caused a decrease of NCPCs in the wound and aberrant skin repair. These data demonstrate that Sox2 regulates skin repair, likely by controlling NCPCs, and raise the possibility that nerve-derived NCPCs may play a general role in mammalian tissue repair.

Perivascular-Derived Stem Cells with Neural Crest Characteristics Are Involved in Tendon Repair

“…However, we could not detect the expression of Sox10 and Snail, the other two markers for NCSCs, both in the native tendon and injured tendon (data not shown). This could be due to the activation of these stem cells after they are isolated and cultured, which are similar to other investigations [27,28].…”

Wound repair: a showcase for cell plasticity and migration

“…For example, multipotent bone marrow-derived mesenchymal stem cells (MSCs) [70,71] appear to be recruited to sites of tissue injury. These, or even other multipotent cell populations [72], could be already residing in the skin (e.g. peri-vascularly or in the adipose tissue [73,74]), or circulating as with "fibrocytes" [75,76] and recruited to the site of injury in a manner similar to leukocytes.…”

Bacterial-induced cell reprogramming to stem cell-like cells: new premise in host–pathogen interactions

“…It is known that the fate of somatic cells can be altered by forced expressions of Hox genes [43]. On the other hand, Sox2, as described above, is a critical TF involved in maintaining embryonic stem (ES) stem cells, neural stem cells and neural crest stem cells, as well as one of the factors required for reprogramming fibroblasts to induced pluripotent stem (iPS) cells with ES cell-like properties [16, 44,45,46,47], suggesting good reasons why ML target these embryonic TFs during Schwann cell reprogramming. An important finding is that these ML-induced events are not associated with the tumor suppressor genes like p53 or Schwann cell tumor associated gene NF1, which is inactivated in neurofibromatosis type 1, suggesting reprogramming events in Schwann cells are not associated with tumor formation [36].…”