Abstract
Stem cells of the neural crest (NC) vitally participate to embryonic development, but also remain in distinct niches as quiescent neural crest-derived stem cell (NCSC) pools into adulthood. Although NCSC-populations share a high capacity for self-renewal and differentiation resulting in promising preclinical applications within the last two decades, inter- and intrapopulational differences exist in terms of their expression signatures and regenerative capability. Differentiation and self-renewal of stem cells in developmental and regenerative contexts are partially regulated by the niche or culture condition and further influenced by single cell decision processes, making cell-to-cell variation and heterogeneity critical for understanding adult stem cell populations. The present review summarizes current knowledge of the cellular heterogeneity within NCSC-populations located in distinct craniofacial and trunk niches including the nasal cavity, olfactory bulb, oral tissues or skin. We shed light on the impact of intrapopulational heterogeneity on fate specifications and plasticity of NCSCs in their niches in vivo as well as during in vitro culture. We further discuss underlying molecular regulators determining fate specifications of NCSCs, suggesting a regulatory network including NF-κB and NC-related transcription factors like SLUG and SOX9 accompanied by Wnt- and MAPK-signaling to orchestrate NCSC stemness and differentiation. In summary, adult NCSCs show a broad heterogeneity on the level of the donor and the donors’ sex, the cell population and the single stem cell directly impacting their differentiation capability and fate choices in vivo and in vitro. The findings discussed here emphasize heterogeneity of NCSCs as a crucial parameter for understanding their role in tissue homeostasis and regeneration and for improving their applicability in regenerative medicine.
Highlights
INTRAPOPULATIONAL HETEROGENEITY OF ADULT STEM CELLSAdult stem cells (ASCs) are undifferentiated cells capable of self-renewal as well as multi-lineage differentiation and are located in a broad range of niches throughout the human body (Rochat et al, 1994; Johansson et al, 1999; Pittenger et al, 1999; Messina et al, 2004; Hauser et al, 2012; Höving et al, 2020b)
NCSC-heterogeneity was reported to be present on multiple levels including the donor, the sex of the donor, the cell population and the single stem cell
Interpopulational differences further substantially contribute to the heterogeneity between NCSCs observed in differentiation potential with regard to their niche of origin
Summary
INTRAPOPULATIONAL HETEROGENEITY OF ADULT STEM CELLSAdult stem cells (ASCs) are undifferentiated cells capable of self-renewal as well as multi-lineage differentiation and are located in a broad range of niches throughout the human body (Rochat et al, 1994; Johansson et al, 1999; Pittenger et al, 1999; Messina et al, 2004; Hauser et al, 2012; Höving et al, 2020b). AND OUTLOOK: NCSC-IDENTITIES BETWEEN HETEROGENEOUS DIFFERENTIATION POTENTIAL AND COMMON TRANSCRIPTIONAL SIGNATURES
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