Neural Stem Cells (NSCs) and Proteomics

Abstract

Neural stem cells (NSCs) can self-renew and give rise to the major cell types of the CNS. Studies of NSCs include the investigation of primary, CNS-derived cells as well as animal and human embryonic stem cell (ESC)-derived and induced pluripotent stem cell (iPSC)-derived sources. NSCs provide a means with which to study normal neural development, neurodegeneration, and neurological disease and are clinically relevant sources for cellular repair to the damaged and diseased CNS. Proteomics studies of NSCs have the potential to delineate molecules and pathways critical for NSC biology and the means by which NSCs can participate in neural repair. In this review, we provide a background to NSC biology, including the means to obtain them and the caveats to these processes. We then focus on advances in the proteomic interrogation of NSCs. This includes the analysis of posttranslational modifications (PTMs); approaches to analyzing different proteomic compartments, such the secretome; as well as approaches to analyzing temporal differences in the proteome to elucidate mechanisms of differentiation. We also discuss some of the methods that will undoubtedly be useful in the investigation of NSCs but which have not yet been applied to the field. While many proteomics studies of NSCs have largely catalogued the proteome or posttranslational modifications of specific cellular states, without delving into specific functions, some have led to understandings of functional processes or identified markers that could not have been identified via other means. Many challenges remain in the field, including the precise identification and standardization of NSCs used for proteomic analyses, as well as how to translate fundamental proteomics studies to functional biology. The next level of investigation will require interdisciplinary approaches, combining the skills of those interested in the biochemistry of proteomics with those interested in modulating NSC function.

Fig. 1.

Illustration of the primary means of obtaining neural stem cells (NSCs). Pluripotent stem cells such as (A) embryonic stem cells (ESCs) obtained from the blastocyst or (B) induced pluripotent stem cells (iPSCs) derived from mature somatic cells can be directed to a neural stem cell fate in culture to generate NSCs. NSCs can also be isolated directly from (C) the developing neural tube, (D) the developing nervous system, or (E) from the adult CNS. The type of NSCs obtained is a function of both in vivo regional and temporal aspects as well as the in vitro environment the cells experience, as represented by the varying color and shape of the NSCs. CNS: central nervous system; SC: spinal cord. Not drawn to scale.