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Li C.,Agresearch Ltd. | Li C.,State Key Laboratory for Molecular Biology of Special Economic Animals
Birth Defects Research Part C - Embryo Today: Reviews | Year: 2012

Full regeneration of deer antlers, a bona fide epimorphic process in mammals, is in defiance of the general rule of nature. Revealing the mechanism underlying this unique exception would place us in a better position to promote organ regeneration in humans. Antler regeneration takes place in yearly cycles from its pedicle, a permanent protuberance on the frontal bone. Both growing antlers and pedicles consist of internal (cartilage and bone) and external components (skin, blood vessels, and nerves). Recent studies have demonstrated that the regeneration of both internal and external components relies on the presence of pedicle periosteum (PP). PP cells express key embryonic stem cell markers (Oct4, Nanog, and SOX2) and are multipotent, so are termed antler stem cells. Now it is clear that proliferation and differentiation of PP cells directly forms internal antler components; however, how PP initiates and maintains the regeneration of external antler components is thus far not known. Based on the direct as well as indirect evidence that is presented in this review, I put forward the following hypothesis to address this issue. The full regenerative ability of external antler tissue components is achieved through PP-derived chemical induction and PP-derived mechanical stimulation: the former triggers the regeneration of these external components, whereas the latter drives their rapid elongation. Eventual identification of the putative PP-derived chemical factors would open up a new avenue for devising effective therapies for lesions involving each of these tissue components, be they traumatic, degenerative, or linked to developmental (genetic) anomalies. © 2012 Wiley Periodicals, Inc.

Deb-Choudhury S.,Agresearch Ltd. | Wang W.,Agresearch Ltd. | Clerens S.,Agresearch Ltd. | McMahon C.,Agresearch Ltd. | And 3 more authors.
Molecular and Cellular Biochemistry | Year: 2015

The astonishing growth rate of deer antlers offers a valuable model for the discovery of novel factors and regulatory systems controlling rapid tissue growth. Numerous molecules have been identified in growing antlers using a variety of techniques. However, little is known about the spatial distribution of these molecules in situ. A technique that has the potential to help in this regard is direct proteomic analysis of tissue sections by matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS). The present study applied this technique to spatially map molecules in antler tissue sections. Two protonated molecular ions were selected: m/z 6679 and m/z 6200 corresponding to VEGF and thymosin beta-10, respectively. Superimposition of the respective ion images on to histologically stained samples showed distinct spatial distribution across the antler tissue sections which were consistent with the previous reports using in situ hybridization. Two other molecular ions specifically m/z 8100 and m/z 11,800 were also selected, corresponding to reported masses of urocortin precursor and thioredoxin, respectively. As the spatial distribution of these proteins is not specifically known, MALDI-IMS was used as a potential technique to obtain information on their distribution on antler tips. The presence of all these molecules in deer antlers were further confirmed using LC–MS/MS data. The present study also demonstrated that MALDI-IMS could be further used to image antler sections with an extended ion mass range of up to m/z 45,000, thus potentially increasing the ability to discover the distribution of a larger set of molecules that may play an important role in antler growth. We have thus demonstrated that MALDI-IMS is a promising technique for generating molecular maps with high spatial resolution which can aid in evaluating the function of novel molecules during antler growth. © 2015, Springer Science+Business Media New York.

Li C.,Agresearch Ltd. | Li C.,State Key Laboratory for Molecular Biology of Special Economic Animals | Harper A.,Agresearch Ltd. | Puddick J.,University of Waikato | And 2 more authors.
PLoS ONE | Year: 2012

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. © 2012 Li et al.

Luo W.,Jilin University | Luo W.,State Key Laboratory for Molecular Biology of Special Economic Animals | Luo W.,Chinese Academy of Agricultural Sciences | Li Z.,Jilin University | And 9 more authors.
Cellular Physiology and Biochemistry | Year: 2014

Background/Aims: Optimal use of Cre mediated recombination in conditional animal models depends on well characterized Cre driver lines. Unfortunately, some Cre driver lines exhibit unexpected expression patterns hindering their utility in Cre/loxP systems. Thus, systematic assessment of new Cre lines is essential for generating useful Cre driver lines for future studies.Methods: Here, we describe a Cre Transgenic (Tg) mini-pig line in which the expression of Cre is directed by a 3-kb 5' fragment of the kidney-specific aquaporin 2 (AQP2); however, the AQP2-Cre Tg mini-pig line exhibits expression of Cre in alveolar epithelial cells (AECs) instead of collecting duct cells. The specificity of the AQP2-Cre plasmid was validated in vitro, and indicating that the AQP2-Cre was specifically expressed in the transfected LLC-PK1 cells. Absolute quantitative real-time PCR (qRT-PCR) and inverse PCR were performed to determine the copy numbers and integration sites of the AQP2-Cre transgene. Relative qRT-PCR was performed to evaluate variation in Cre expression levels over time.Results: Our data indicated that this AQP2-Cre Tg mini-pig line exhibits stable expression of Cre recombinase over time and in subsequent generations, even though the AQP2-Cre transgene was segregated and reduced in subsequent generations.Conclusion: Combined with our previous studies of the activity of this Cre, we conclude that this Cre Tg mini-pig line will provide a reliable tool for generating lung-specific gene targeting mini-pig models, thereby allowing the investigation of gene functions in lung development and studying the molecular mechanisms of human lung disease. Copyright © 2014 S. Karger AG, Base.

Li C.,State Key Laboratory for Molecular Biology of Special Economic Animals | Li C.,Chinese Academy of Agricultural Sciences | Zhao H.,State Key Laboratory for Molecular Biology of Special Economic Animals | Zhao H.,Chinese Academy of Agricultural Sciences | And 3 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2014

Deer antler is the only mammalian organ that can fully grow back once lost from its pedicle - the base from which it grows. Therefore, antlers probably offer the most pertinent model for studying organ regeneration in mammals. This paper reviews our current understanding of the mechanisms underlying regeneration of antlers, and provides insights into the possible use for human regenerative medicine. Based on the definition, antler renewal belongs to a special type of regeneration termed epimorphic. However, histological examination failed to detect dedifferentiation of any cell type on the pedicle stump and the formation of a blastema, which are hallmark features of classic epimorphic regeneration. Instead, antler regeneration is achieved through the recruitment, proliferation and differentiation of the single cell type in the pedicle periosteum (PP). The PP cells are the direct derivatives of cells resident in the antlerogenic periosteum (AP), a tissue that exists in prepubertal deer calves and can induce ectopic antler formation when transplanted elsewhere on the deer body. Both the AP and PP cells express key embryonic stem cell markers and can be induced to differentiate into multiple cell lineages in vitro and, therefore, they are termed antler stem cells, and antler regeneration is a stem cell-based epimorphic regeneration. Comparisons between the healing process on the stumps from an amputated mouse limb and early regeneration of antlers suggest that the stump of a mouse limb cannot regenerate because of the limited potential of periosteal cells in long bones to proliferate. If we can impart a greater potential of these periosteal cells to proliferate, we might at least be able to partially regenerate limbs lost from humans. Taken together, a greater understanding of the mechanisms that regulate the regeneration of antlers may provide a valuable insight to aid the field of regenerative medicine. This article is part of a Directed Issue entitled: Regenerative Medicine: the challenge of translation. © 2014 Elsevier Ltd.

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