Proteomic Profiling of Stem Cell Tissues during Regeneration of Deer Antler: A Model of Mammalian Organ Regeneration

As the only known
mammalian organ that can fully and annually regenerate,
deer antler has significant advantages over lower-order animal models
when investigating the control of stem-cell-based organ regeneration.
Antler regeneration is known to be initiated and maintained by neural-crest-derived
stem cells in different states of activation. Antler stem cells can
therefore be used as a model to study proteins and pathways involved
in the maintenance of a stem cell niche and their activation and differentiation
during organ formation. In this study, the MSC markers CD73, CD90,
and CD105 were examined within the antler tip. Label-free quantification
was performed to investigate the protein profiles of antler stem cells
under different stages of activation and included dormant pedicle
periosteum (DPP), antler growth center (GC), post-active stem cells
from mid-beam antler periosteum (MAP), and deer facial periosteum
(FP) as a control (n = 3 per group). PEAKS and IPA
software were used to analyze the proteomic data. Our research confirmed
the central role of stem cell activation in the development of this
mammalian organ by localizing the MSC markers within the antler growth
center. Label-free quantification revealed that the greatest number
of unique proteins (87) was found in the growth center. There were
only 12 proteins found with expression levels that significantly differed
between DPP and FP. Protein profiles of these two groups indicated
that antler stem cells may use similar mechanisms to maintain dormancy
within a stem cell niche. The number of significantly regulated proteins
among DPP, MAP, and GC was 153. Among them, the majority were upregulated
in the growth center. Activation of antler stem cells was associated
with many biological processes and signaling pathways, such as Hippo
and canonical Wnt signaling. This work identifies the key pathways,
molecular/cellular functions, and upstream regulators involved in
mammal organ regeneration. The mass spectrometry proteomics data have
been deposited to the ProteomeXchange
Consortium via the iProX partner repository with the dataset
identifier PXD016824.