On the road again: Establishment and maintenance of stemness in the neural crest from embryo to adulthood

Abstract

Unique to vertebrates, the neural crest (NC) is an embryonic stem cell population that contributes to a greatly expanding list of derivatives ranging from neurons and glia of the peripheral nervous system, facial cartilage and bone, pigment cells of the skin to secretory cells of the endocrine system. Here, we focus on what is specifically known about establishment and maintenance of NC stemness and ultimate fate commitment mechanisms, which could help explain its exceptionally high stem cell potential that exceeds the “rules set during gastrulation.” In fact, recent discoveries have shed light on the existence of NC cells that coexpress commonly accepted pluripotency factors like Nanog, Oct4/PouV, and Klf4. The coexpression of pluripotency factors together with the exceptional array of diverse NC derivatives encouraged us to propose a new term “pleistopotent” (Greek for abundant, a substantial amount) to be used to reflect the uniqueness of the NC as compared to other post-gastrulation stem cell populations in the vertebrate body, and to differentiate them from multipotent lineage restricted stem cells. We also discuss studies related to the maintenance of NC stemness within the challenging context of being a transient and thus a constantly changing population of stem cells without a permanent niche. The discovery of the stem cell potential of Schwann cell precursors as well as multiple adult NC-derived stem cell reservoirs during the past decade has greatly increased our understanding of how NC cells contribute to tissues formed after its initial migration stage in young embryos.

Single cell transcriptomic and spatial landscapes of the developing human pancreas

“…It has been suggested that neural crest cells, the precursors of Schwann cells, directly differentiate into islet cells in mice (Pearse and Polak, 1971), but rats that lack Schwann cells progenitors do not fail to develop an endocrine pancreas (Pictet et al, 1976). Nonetheless, the plasticity of Schwann cell precursors in pancreas development is not fully appreciated and they have been implicated in cell specification in other tissues (Perera and Kerosuo, 2021). We have shown here that a Schwann cell subset, the immature Schwann cells, express L1CAM and are located in spatial proximity to endocrine progenitors, with local hotspots of L1CAM-EPHB2 interactions.…”

Dental Pulp Stem Cell Heterogeneity: Finding Superior Quality “Needles” in a Dental Pulpal “Haystack” for Regenerative Medicine-Based Applications

“…Under basal conditions, hDPSCs express osteogenic marker genes, including runt-related transcription factor 2 (RUNX2), type I collagen, dentine sialophosphoprotein (DSPP), osteocalcin, osteopontin, osteonectin, alkaline phosphatase, and bone morphogenetic proteins (BMP-2, BMP-4); adipogenic marker genes, such as peroxisome proliferator-activated receptor γ (PPAR γ ), lipoprotein lipase (LPL), leptin, and adipophilin; chondrogenic markers, such as type II collagen and SOX9; and myogenic markers, such as α SMA, myosin, myogenin, and desmin [ 2 , 6 – 8 , 12 , 49 ]. Such genotypic qualities support the extensive plasticity displayed by hDPSCs, a hallmark feature which makes these populations such attractive propositions in regenerative medicine, in terms of their potential to mature into more specialised cells for the potential repair of dental and nondental tissues throughout the body [ 11 , 15 , 27 – 29 ]. Under appropriate inductive conditions in vitro , hDPSCs can be induced to undergo differentiation into numerous cell types associated with both mesodermal and nonmesodermal (ectodermal and endodermal) lineages, including odontoblasts, osteoblasts, chondrocytes, adipocytes, glia cells, neuronal cells, oligodendrocytes, Schwann cells, retinal ganglion-like cells, endothelial cells, pancreatic cells, cardiomyocytes, hepatocytes, melanocytes, skeletal muscle cells, and bladder smooth muscle cells [ 8 – 12 , 15 , 50 ], well beyond the minimum multilineage differentiation criteria stipulated for hBMMSCs by the ISCT [ 47 ].…”

“…Despite dental pulp being recognised as a highly vascularised and innervated tissue comprising of a multi-heterogeneous population of cells [ 1 ], hDPSCs are established to be ectomesenchymal-derived stem cells, originating during embryonic tooth development from migrating cranial neural crest cells and possessing MSC-related properties [ 26 – 29 ]. During development, neural crest-derived cells delaminate from the periphery of the neural tube, migrate to the oral region, and undergo epithelial-mesenchymal transition, differentiating into neural crest stem cells and subsequently into several other cell types and tissues within the craniofacial region ( Figure 1 ).…”

“…Another essential facet of hDPSC stemness, which makes them appealing options for regenerative medicine, is their potential multipotency capabilities [ 11 , 15 , 27 – 29 ]. Consequently, a wide range of studies have implicated individual or collections of cell surface markers as being indicative of multipotent differentiation characteristics in hDPSC subpopulations, including STRO-1 + /CD146 + [ 59 , 80 ], c-kit + /CD34 + /STRO-1 + [ 50 , 81 – 83 ], CD51 + /CD140 α + [ 64 ], CD105 + [ 89 ], CD271 − [ 52 , 53 , 64 , 65 , 83 ], CXCR4 + [ 57 , 91 , 92 ], and IGF1R + [ 94 ].…”

“…Gronthos et al [ 6 , 7 ] originally proposed that the heterogeneous nature of hDPSCs may reflect differences in their developmental stages or may even represent different pulpal cell lineages. Since then, studies into the developmental potentials of different hDPSC clones have suggested that a number of subpopulations exist within the dental pulp, derived from either the mesoderm or ectoderm of migratory cranial neural crest cell origins [ 26 – 29 , 64 , 83 ]. Several studies indicate that intrinsic positional information can dictate the neural crest stem cell phenotype within tissues and that environmental signals can regulate neural crest cell developmental fate and differentiation.…”