Neural-Competent Cells of Adult Human Dermis Belong to the Schwann Lineage

H Y P O T H E S I S L E T T E R3. Although loss of Nf1 is required for neurofibroma development, it is not sufficient and tumor microenvironment plays a key role in this process. Poorly regulated wound healing has been described in NF1 haploinsufficient tissues, S8 again highlighting a possible relationship between wounding and tumor initiation. | HYPOTHESISIn the skin, terminal SCs ensheathe peripheral nerve endings. S9These SCs are able to dedifferentiate into a progenitor-like state in response to trauma or other insults. 6-8 Furthermore, recent data from our group suggest terminal SCs may behave as bona fide dermal stem cells. 9 Based on all of these premises, we hypothesize that dedifferentiation of SCs could originate human dNFs. | EVIDENCE SUPPORTING THIS HYPOTHESISWe analysed the differentiation stage of dNFs of 8 patients diagnosed with NF1 (Data S1), looking at the expression levels of genes characteristic of the different dermal stem cell stages by qRT-PCR of isolated tumor tissue (Fig. 1a,b). 9 We found that SC markers SOX10 and S100B were upregulated in 100% and 75% of tumors, respectively (Fig. 1c). Interestingly, NGFR, NCAM1 and SOX2, all of them dermal stem cell markers were present in tumors although in variable numbers (Fig. 1d). In contrast, MCAM and SOX9 which mark more differentiated stages were mostly nonexpressed in tumors (Fig. 1e). CDH19, a marker of Schwann cell precursors and adult dermal stem cells, was upregulated in 100%(8/8) of the cases (Fig. 1f). Levels of neurofibromin (NF1) were unaltered (75%) or slightly upregulated (25%; data not shown).To confirm CDH19 expression at the protein level, we analysed dNF and unaffected skin sections of NF1 patients as well as healthy donor skin by immunofluorescence. We confirmed upregulation of CDH19 in dNFs as compared to controls (Fig. S1). The difference was especially clear in the lower dermis, where most lesional NGFR + , S100β + , and SOX10 + cells are present ( Figs S2-S4). We also observed that S100β + /NGFR + early stage microneurofibromas were present in "unaffected" NF1 patient skin and that, interestingly, CDH19 was also HypotHesis Letter 902 | upregulated in those areas (Fig. S5). Finally, we pursued characterization of CDH19 expression by immunofluorescence in dermal spheres isolated from control foreskin and dNFs. As expected, CDH19 + cells were detected in both normal and dNF-derived spheres (Fig. S6). In these animals, we predict that dedifferentiation of SCs would produce dNFs even in the absence of resident dermal stem cells. | HOW TO TEST THIS HYPOTHESIS | RELEVANCE AND PERSPECTIVESOur preliminary results are consistent with dermal regeneration via SC dedifferentiation playing a role in dNF initiation. Further work is needed in order to confirm these preliminary results in a higher number of patients and to elucidate the molecular mechanisms behind the SC dedifferentiation process, to further illuminate our understanding of human dNF development. ACKNOWLEDGEMENTS CONFLICT OF INTERESTSThe authors have declared no conflicti...

show abstract

“…1a,b). 9 We found that SC markers SOX10 and S100B were upregulated in 100% and 75% of tumors, respectively ( Fig. 1c).…”

Section: Evidence Supporting This Hypothesismentioning

confidence: 72%

“…[6][7][8] Furthermore, recent data from our group suggest terminal SCs may behave as bona fide dermal stem cells. 9 Based on all of these premises, we hypothesize that dedifferentiation of SCs could originate human dNFs.…”

Section: Hypothesismentioning

confidence: 99%

Does Schwann cell dedifferentiation originate dermal neurofibromas?

Iribar

Jaka

Ormaechea

et al. 2016

Experimental Dermatology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The immediate progeny of NC-BCs, together with other nerve-associated SCPs, migrate along the sensory nerves toward the skin to give rise to highly specialized glial cells (denominated specific sensory nerve fiber-associated glia in the skin) associated to nerve endings in the epidermis although these cells are distinct to the specialized glial subtype found within the cutaneous sensory corpuscles [24]. But according to Etxaniz and coworkers [25], in the skin BC derivatives give rise to at least three glial populations: Schwann cells (mainly nonmyelinating) associated with subcutaneous and dermal nerves and two types of terminal Schwann cells, associated with lanceolate endings or free nerve endings. It can be speculated that the glial cells of sensory corpuscles can derivate of that first type.…”

Section: Origin Of the Sensory Corpuscles Glial Cellsmentioning

confidence: 99%

The Glial Cell of Human Cutaneous Sensory Corpuscles: Origin, Characterization, and Putative Roles

Cobo¹,

García‐Mesa²,

García‐Piqueras³

et al. 2020

Somatosensory and Motor Research

View full text Add to dashboard Cite

Sensory corpuscles of human skin are structures located at the peripheral end of the mechanoreceptive neurons and function as low-threshold mechanoreceptors (LTMRs). In its structure, in addition to the axon, there are glial cells, not myelinating, that are organized in different ways according to the morphotype of sensitive corpuscle, forming the so-called laminar cells of Meissner's corpuscles, the laminar cells of the inner core of Pacinian corpuscles, or cells of the inner core in Ruffini's corpuscles. Classically the glial cells of sensory corpuscles have been considered support cells and passive in the process of mechanotransduction. However, the presence of ion channels and synapses-like systems between them and the axon suggests that corpuscular glial cells are actively involved in the transformation of mechanical into electrical impulses. This chapter is an update on the origin, development, cytoarchitecture, and protein profile of glial cells of sensitive corpuscles especially those of human glabrous skin.

show abstract

“…Skin-derived precursor cells (SKPs) can also differentiate into glial, epidermal, and dermal cell types [112]. SKPs then, too, could be used as a type of cell-based wound therapy [113,114,115]. In fact, there may be multiple sources of precursor cells within the hair follicle that contribute to wound healing [116].…”

Section: Experimental Biomaterials and Future Directionsmentioning

confidence: 99%

Minimizing Skin Scarring through Biomaterial Design

Moore

Longaker

2017

JFB

View full text Add to dashboard Cite

Wound healing continues to be a major burden to patients, though research in the field has expanded significantly. Due to an aging population and increasing comorbid conditions, the cost of chronic wounds is expected to increase for patients and the U.S. healthcare system alike. With this knowledge, the number of engineered products to facilitate wound healing has also increased dramatically, with some already in clinical use. In this review, the major biomaterials used to facilitate skin wound healing will be examined, with particular attention allocated to the science behind their development. Experimental therapies will also be evaluated.

show abstract

Neural-Competent Cells of Adult Human Dermis Belong to the Schwann Lineage

Cited by 40 publications

References 51 publications

Does Schwann cell dedifferentiation originate dermal neurofibromas?

Does Schwann cell dedifferentiation originate dermal neurofibromas?

The Glial Cell of Human Cutaneous Sensory Corpuscles: Origin, Characterization, and Putative Roles

Minimizing Skin Scarring through Biomaterial Design

Contact Info

Product

Resources

About