Proteomes and Signalling Pathways of Antler Stem Cells

Chunyi Li,Anne Harper,Chris Mcmahon,Wenying Wang,Jonathan Puddick,Andreas Bergmann

doi:10.1371/journal.pone.0030026

Abstract

As the only known example of complete organ regeneration in mammals, deer antler in the growing or velvet phase is of major interest in developmental biology. This regeneration event initiates from self-renewing antler stem cells that exhibit pluripotency. At present, it remains unclear how the activation and quiescence of antler stem cells are regulated. Therefore, in the present study proteins that were differentially expressed between the antler stem cells and somatic cells (facial periosteum) were identified by a gel-based proteomic technique, and analysed using Ingenuity Pathway Analysis software. Several molecular pathways (PI3K/Akt, ERK/MAPK, p38 MAPK, etc.) were found to be activated during proliferation. Also expressed were the transcription factors POU5F1, SOX2, NANOG and MYC, which are key markers of embryonic stem cells. Expression of these proteins was confirmed in both cultured cells and fresh tissues by Western blot analysis. Therefore, the molecular pathways and transcription factors identified in the current study are common to embryonic and adult stem cells. However, expression of embryonic stem cell transcription factors would suggest that antler stem cells are, potentially, an intermediary stem cell type between embryonic and the more specialized tissue-specific stem cells like those residing in muscle, fat or from a hematopoietic origin. The retention of this embryonic, pluripotent lineage may be of fundamental importance for the subsequent regenerative capacity of antlers.

Highlights

The annual full regeneration of deer antlers is unique among mammals and the evidence to date indicates that it is a stem cell based process [1,2,3]
Growth of the pedicle itself is initiated during puberty from a different pool of stem cells located in a zone named the antlerogenic periosteum (AP cells; Figure S1C), which covers a crest in the deer skull located just above the eye socket [12]
Tissue sampling Antlerogenic periosteum (AP), PP and FP were collected from red deer heads immediately after slaughtering in May and October, according to the protocol described by Li and Suttie [20]

Summary

Introduction

The annual full regeneration of deer antlers is unique among mammals and the evidence to date indicates that it is a stem cell based process [1,2,3]. Deer antler provides a single organ model in which growth and development are controlled by the proliferation and differentiation of tissue specific stem cells with embryonic like properties [8,9]. A recent study [10] showed that the pool of stem cells from which antler regeneration initiates resides in the periosteum of a permanent bony extension from the deer skull termed the pedicle (Figure S1A). Pedicles that are deprived of the enveloping periosteum do not regenerate antlers (Figure S1B). Growth of the pedicle itself is initiated during puberty from a different pool of stem cells located in a zone named the antlerogenic periosteum (AP cells; Figure S1C), which covers a crest in the deer skull located just above the eye socket [12]. Removal of the AP prior to pedicle initiation stops pedicle and antler growth, while transplantation of the AP induces ectopic pedicle and antler formation (Figure S1D; 10–12)

Methods

Results

Conclusion