Molecular Characterization of Embryonic Stem Cell-Derived Cardiac Neural Crest-Like Cells Revealed a Spatiotemporal Expression of an Mlc-3 Isoform

Abstract

Background and Objectives: Pluripotent embryonic stem (ES) cells represent a perfect model system for the investigation of early developmental processes. Besides their differentiation into derivatives of the three primary germ layers, they can also be differentiated into derivatives of the 'fourth' germ layer, the neural crest (NC). Due to its multipotency, extensive migration and outstanding capacity to generate a remarkable number of different cell types, the NC plays a key role in early developmental processes. Cardiac neural crest (CNC) cells are a subpopulation of the NC, which are of crucial importance for precise cardiovascular and pharyngeal glands' development. CNC-associated malformations are rare, but always severe and life-threatening. Appropriate cell models could help to unravel underlying pathomechanisms and to develop new therapeutic options for relevant heart malformations. Methods: Murine ES cells were differentiated according to a mesodermal-lineage promoting protocol. Expression profiles of ES cell-derived progeny at various differentiation stages were investigated on transcript and protein level. Results: Comparative expression profiling of murine ES cell multilineage progeny versus undifferentiated ES cells confirmed differentiation into known cell derivatives of the three primary germ layers and provided evidence that ES cells have the capacity to differentiate into NC/CNC-like cells. Applying the NC/CNC cell-specific marker, 4E9R, an unambiguous identification of ES cell-derived NC/CNC-like cells was achieved. Conclusions: Our findings will facilitate the establishment of an ES cell-derived CNC cell model for the investigation of molecular pathways during cardiac development in health and disease.

Direct Conversion to Achieve Glial Cell Fates: Oligodendrocytes and Schwann Cells

“…Schwann cells originate from multipotent migratory neural crest cells that are specified at the neural plate border region and differentiate into neurons and glia in the PNS. Most of the early developmental studies on neural crest cells and Schwann cells have been primarily conducted in different organisms because of the spatiotemporal properties of neural crest cells during embryonic development ( 49 , 50 ). Developmental mouse embryos have been sacrificed to study neural crest biology ( 51 , 52 ) and avian models such as quail and chick that are capable of tracking live neural crest cells also have been commonly used ( 53 ).…”

Bioactive Molecular Discovery Using Deer Antlers as a Model of Mammalian Regeneration

“…Embryonic stem cells (ESCs) originate from the zygote, and differentiate into the four different germ layers: endoderm, mesoderm, ectoderm, and neural crest. − The four germ layers have multipotent capacity and can produce differentiated cells for specific organs and tissues. Adult stem cells residing within organs/tissues derived from different germ layers possess the lowest differentiation capacity in the mammalian stem cell lineage; however, they play important roles during physiological cell turnover and mild injury repair in the adult, such as hepatocyte replication and bone fracture healing. − It is however still difficult to accurately identify organ specific stem cells, and some even remain disputed, such as the existence of “cardiac stem cells”. , Their ability to drive repair and regeneration is also not static, and in mammals it is attenuated with aging .…”