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February 10, 2021 // --- Cell differentiation is often described as a one-way process through a series of genealogical restriction events, and as the embryo develops, the cell's differentiation potential becomes smaller and smaller, a concept that is well known in Conrad Waddington's overt genetic landscape.
, however, a vertebrate-specific transient cell population called cranial neural crest cells (CNCC) challenges this pattern.
Although CNCC originates in the outer embryo layer and can differentiate into the typical cell types of this outer embryo layer, they can also produce interstate cell types associated with the mesothromat genealogy, such as bone cells, cartilage cells, and smooth muscle cells.
how the CNCC extends their differentiation potential beyond the embryonic layers of their origin remains unresolved.
In a new study, researchers from Stanford University School of Medicine in the United States speculated that an impartial analysis of transcriptional heterogeneity in the early stages of mammalian CNCC development might identify a pregenital cell population and provide clues as to how these particular cells can gain their extraordinary differentiation potential.
to test this, they combined single-cell RNA sequencing analysis of CNCC in staged mouse embryos with subsequent genealogy tracking, loss of function, and observational genomic analysis experiments.
study was published in the February 5, 2021 issue of the journal Science under the title "Reactivation of the pluripotency program program firsts formation of the cranial neural crest."
images from Science, 2021, doi:10.1126/science.abb4776.
They found that the pre-migration CNCC was heterogeneic and carried location information that reflected its origin in the neurosethic, but this early location information was then erased, and the CNCC, where the location information was erased, exhibited relatively uniform transcription characteristics, which were later re-diversified as the CNCC experienced the first cellization.
they identified an early group of prescellular cells that expressed typical erythrogen transcription factors and produced CNCC and craniofacial structures.
pl potient factor Oct4 is not maintained by the outer embryo layer, but is briefly reactivated in the expected CNCC after the head folds are formed, and as development progresses, its expression is transferred from the front of the cranial region to the back.
Oct4 is not necessary for CNCC induction in the neurosethics, but it is important for the morphology and survival of facial mesenchyme, which directly corred this erythrogen factor with the expansion of CNCC cell potential.
the open chromatin landscape of Oct4-positive CNCC pregenital cells is consistent with its neurosethic origin, and is also broadly similar to that of erythromat endosome stem cells (epiblast stem cells).
, they observed activation of a portion of the far-end regulatory regions at genomic bits associated with future neural crucible migration and interstuming formation.
These results show that pre-migration CNCC first forms a heterogeneic group that rapidly changes their transcriptional identity during locational information erasing, resulting in a relatively uniform (and possibly functional) cell population that can adapt to future locations during and after migration.
functional ethonism and plasticity of CNCC are consistent with previous embryology studies.
addition, evidence that CNCC prescient cells briefly reactivate erratic factors suggests that these cells underwent a natural in vivo reprogramming event that allowed them to follow Waddington's supernatural genetic landscape.
fact, the results of this study suggest that at least one plurogen, Oct4, is necessary to expand the developmental potential of CNCC, including facial interstumal formation.
whether this mechanism applies only to CNCC and whether this expansion of cell plasticity can be used for regenerative medicine remains an interesting question for future research.
(Bioon.com) Reference: Antoine Zalc et al. Reactivation of the pluripotency program precedes formation of the cranial neural crest. Science, 2021, doi:10.1126/science.abb4776.