Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates

Neural crest (NC) cells are a stem-like multipotent population of progenitor cells that are present in vertebrate embryos, traveling to various regions in the developing organism. Known as the "fourth germ layer", these cells originate in the ectoderm between the neural plate (NP), which will become the brain and spinal cord, and nonneural tissues that will become the skin and the sensory organs. NC cells can differentiate into more than 30 different derivatives in response to the appropriate signals including, but not limited to, craniofacial bone and cartilage, sensory nerves and ganglia, pigment cells, and connective tissue. The molecular and cellular mechanisms that control the induction and specification of NC cells include epigenetic control, multiple interactive and redundant transcriptional pathways, secreted signaling molecules, and adhesion molecules. NC cells are important not only because they transform into a wide variety of tissue types, but also because their ability to detach from their epithelial neighbors and migrate throughout developing embryos utilizes mechanisms similar to those used by metastatic cancer cells. In this review, we discuss the mechanisms required for the induction and specification of NC cells in various vertebrate species, focusing on the roles of early morphogenesis, cell adhesion, signaling from adjacent tissues, and the massive transcriptional network that controls the formation of these amazing cells. This article is categorized under: Nervous System Development > Vertebrates: General Principles Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Signaling Pathways > Cell Fate Signaling.

show abstract

“…Primarily, non-NC cells (fibroblasts, keratinocytes, etc.) are isolated in vitro (Figure 4b) (V. K. Bajpai et al, 2017).…”

Section: | Signaling Events Regulating Nc Inductionmentioning

confidence: 99%

Specifying neural crest cells: From chromatin to morphogens and factors in between

Rogers

Nie

2018

WIREs Developmental Biology

View full text Add to dashboard Cite

show abstract

“…Recently, in our laboratory, Bajpai et al devised a method to reprogram postnatal human epidermal keratinocytes (KCs) to NClSC (termed KC‐NC) by mimicking signaling events that occur at the neural plate border. Transcriptomic analysis confirmed that epidermally derived NCISCs were similar to those generated from human embryonic stem cells (ESCs) and maintained the multilineage differentiation potential into melanocytes, neurons, SC, and mesenchymal cells in vitro and in ovo . In a subsequent study, we identified the factors that promote expansion of KC‐NC and maintain the NC phenotype.…”

Section: Sources Of Nc‐like Stem Cells In Adult Tissuesmentioning

confidence: 71%

“…Recently, our laboratory showed that cultures of KC from interfollicular epidermis could be the source of NClSCs (termed KC‐NC), after induction with specific chemical cues . KC‐derived NCISCs could be coaxed to differentiate into functional neurons, SC, melanocytes, osteocytes, chondrocytes, adipocytes, and smooth muscle cells in vitro.…”

Section: Ncscs: a Cell Source For The Treatment Of Demyelinating Disomentioning

confidence: 99%

Adult tissue–derived neural crest-like stem cells: Sources, regulatory networks, and translational potential

Mehrotra

Tseropoulos

Bronner

et al. 2019

Stem Cells Translational Medicine

Self Cite

View full text Add to dashboard Cite

Neural crest (NC) cells are a multipotent stem cell population that give rise to a diverse array of cell types in the body, including peripheral neurons, Schwann cells (SC), craniofacial cartilage and bone, smooth muscle cells, and melanocytes. NC formation and differentiation into specific lineages takes place in response to a set of highly regulated signaling and transcriptional events within the neural plate border. Premigratory NC cells initially are contained within the dorsal neural tube from which they subsequently emigrate, migrating to often distant sites in the periphery. Following their migration and differentiation, some NC‐like cells persist in adult tissues in a nascent multipotent state, making them potential candidates for autologous cell therapy. This review discusses the gene regulatory network responsible for NC development and maintenance of multipotency. We summarize the genes and signaling pathways that have been implicated in the differentiation of a postmigratory NC into mature myelinating SC. We elaborate on the signals and transcription factors involved in the acquisition of immature SC fate, axonal sorting of unmyelinated neuronal axons, and finally the path toward mature myelinating SC, which envelope axons within myelin sheaths, facilitating electrical signal propagation. The gene regulatory events guiding development of SC in vivo provides insights into means for differentiating NC‐like cells from adult human tissues into functional SC, which have the potential to provide autologous cell sources for the treatment of demyelinating and neurodegenerative disorders.

show abstract

“…Therefore, cultures of human NC cells can provide a model to study human disease and a source of stem cells for treatment of neurodegenerative diseases that may be currently hindered by the lack of an easily accessible and autologous cell source. Interestingly, recent studies have successfully isolated NC cells from different tissues in the adult body, including the adult hair follicle, craniofacial sources such as the palate and the oral mucosa . Recently, our laboratory showed that NC could be derived from cultures of epidermal KCs isolated from glabrous neonatal foreskin.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, our laboratory showed that NC could be derived from cultures of epidermal KCs isolated from glabrous neonatal foreskin. KC‐derived NC could be coaxed to differentiate into functional neurons, Schwann cells, melanocytes, osteocytes, chondrocytes, adipocytes and smooth muscle cells, in vitro and in vivo, in lineage tracing experiments in chick embryos . Given the accessibility of human skin, KC‐derived NC may provide a valuable source of multipotent stem cells for treatment of myelopathies and other debilitating neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Derivation of neural crest stem cells from human epidermal keratinocytes requires FGF‐2, IGF‐1, and inhibition of TGF‐β1

Tseropoulos

Boroujeni

Bajpai

et al. 2018

Bioengineering & Transla Med

Self Cite

View full text Add to dashboard Cite

Neural crest (NC) cells play a central role in forming the peripheral nervous system, the craniofacial skeleton, and the pigmentation of the skin during development due to their broad multilineage differentiation potential into neurons, Schwann cells, melanocytes, and mesenchymal stem cells. Recently, we identified an easily accessible source of pluripotent NC stem cells from human inter‐follicular keratinocyte (KC) cultures (KC‐NC). In this work, we examined specific conditions for the derivation of NC from KC cultures. More specifically, we examined the role of two growth factors, FGF2 and IGF1, in NC proliferation and in expression of two potent NC transcription factors, Sox10 and FoxD3. Using specific chemical inhibitors, we uncovered that the downstream regulatory pathways AKT/PI3K, MEK/ERK, and JNK/cJun may be critical in Sox10 and FoxD3 regulation in KC‐NC. The TGF‐β1 pathway was also implicated in suppressing Sox10 expression and NC proliferation. In summary, our study shed light into the role of FGF2, IGF1, and TGF‐β1 on the induction of NC from KC cultures and the pathways that regulate Sox10 and FoxD3. We also established culture conditions for sustaining KC‐NC multipotency and, therefore, the potential of these cells for regenerative medicine and cellular therapies.

show abstract

Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates

Cited by 25 publications

References 40 publications

Specifying neural crest cells: From chromatin to morphogens and factors in between

Specifying neural crest cells: From chromatin to morphogens and factors in between

Adult tissue–derived neural crest-like stem cells: Sources, regulatory networks, and translational potential

Derivation of neural crest stem cells from human epidermal keratinocytes requires FGF‐2, IGF‐1, and inhibition of TGF‐β1

Contact Info

Product

Resources

About