State Key Laboratory for Molecular Biology of Special Economic Animals

Jilin, China

State Key Laboratory for Molecular Biology of Special Economic Animals

Jilin, China
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Dong Z.,Chinese Academy of Agricultural Sciences | Ba H.,Chinese Academy of Agricultural Sciences | Ba H.,State Key Laboratory for Molecular Biology of Special Economic Animals | Zhang W.,Chinese Academy of Agricultural Sciences | And 3 more authors.
International journal of molecular sciences | Year: 2016

As the only known organ that can completely regenerate in mammals, deer antler is of real significance in the field of regenerative medicine. Recent studies have shown that the regenerative capacity of the antlers comes from the pedicle periosteum and the cells resident in the periosteum possess the attributes of stem cells. Currently, the molecular mechanism of antler regeneration remains unclear. In the present study, we compared the potentiated and dormant antler stem cells using isobaric tags for the relative and absolute quantification (iTRAQ) labeling of the peptides, coupled with two-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS) to compare the proteome profiles. Proteins were identified by searching against the NCBI nr database and our own Cervine transcriptome database, and bioinformatics analysis was conducted to identify the differentially expressed proteins. Based on this searching strategy, we identified 169 differentially expressed proteins in total, consisting of 70 up- and 99 down-regulated in the potentiated vs. dormant antler stem cells. Reliability of the iTRAQ was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression of selected genes. We identified transduction pathways through the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, such as HIF-1 and PI3K-AKT signaling pathways that play important roles in regulating the regeneration of antlers. In summary, the initiation stage of antler regeneration, a process from dormant to potentiated states in antler stem cells, is regulated by multiple proteins and complicated signal networks.


PubMed | State Kay Laboratory for Molecular Biology of Special Economic Animals and State Key Laboratory for Molecular Biology of Special Economic Animals
Type: | Journal: Frontiers in bioscience (Landmark edition) | Year: 2015

Antlers of the deer are the only mammalian organs that can fully grow back once lost from their pedicles, hence offer the only opportunity to learn how nature has bestowed mammalian epimorphic regeneration. Investigations have demonstrated that it is the proliferation and differentiation of pedicle periosteal cells (PPCs), but not dedifferentiation of the local differentiated cells, that give rise to the antler blastema. PPCs express key embryonic stem cell markers and can be induced to differentiate into multiple cell lineages, so are termed antler stem cells. Further research has found that PPCs can initiate antler regeneration only when they have interacted with cells of the pedicle skin. Histologically, the process of early antler regeneration resembles that of healing of a mouse leg stump wound. However what sets these two apart is the difference in proliferation potential between the PPCs and the periosteal cells of the long bone. We believe that if we can impart a greater proliferation potential to the long bone periosteal cells, we might be able to achieve the dream of regenerating limbs in mammals.


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.,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.


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.


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.


Yang F.,Chinese Academy of Agricultural Sciences | Yang F.,State Key Laboratory for Molecular Biology of Special Economic Animals | Wang W.,Agresearch Ltd. | Li J.,Chinese Institute of Materia Medica | And 4 more authors.
Journal of Experimental Zoology Part B: Molecular and Developmental Evolution | Year: 2011

Antler development is triggered by interactions between antler stem cells resident in the antlerogenic periosteum (AP) and the niche cells in the upper portion of overlying skin mediated by diffusible molecules. These interactive cell populations are interposed by the lower portion of the skin and the subcutaneous loose connective tissue (SLCT). It is known that mechanical deletion of just the central AP (having an area equivalent to the size of a pedicle base) by cutting through the skin and SLCT effectively stimulates the marginal AP to initiate antler development. This study was designed to investigate whether the SLCT layer plays a role in antler development by acting as a physical barrier. The results showed that the marginal AP failed to give rise to an antler after the central AP was cryosurgically destroyed with the preservation of the collagen structure of the SLCT. Furthermore, antler development was significantly advanced when the collagen structures of the skin and SLCT layers were substantially attenuated by repeated sprays with liquid nitrogen while keeping the central AP intact. Therefore, we conclude that the interposing SLCT layer acts as a physical barrier between antler stem cells and the niche cell types, and that timing of antler development is primarily controlled by the permeability of the SLCT layer to the putative interactive diffusible molecules. © 2011 Wiley-Liss, Inc., A Wiley Company.


Sun H.,Chinese Academy of Agricultural Sciences | Sun H.,State Key Laboratory for Molecular Biology of Special Economic Animals | Yang F.,Chinese Academy of Agricultural Sciences | Yang F.,State Key Laboratory for Molecular Biology of Special Economic Animals | And 7 more authors.
PLoS ONE | Year: 2012

Articular cartilage (AC) lacks ability to repair defects due to its avascular nature as healing process relies on cells being brought in by blood vessels. Multiple approaches have been taken to facilitate cartilage repair in clinics, to date there is no effective treatment available that can restores the AC lesion to a normally functioning level over extended periods. In this regard, antler cartilage is unique in being richly vascularised and hence can effectively repair and regenerate. Interestingly, antler stem cells, from which the vascularised cartilage is derived, can form avascular cartilage when taken away from their original niche, suggesting that the vascular or avascular state of antler cartilage is controlled by extrinsic factors. Understanding the mechanisms underlying this phenotype switch may help us to devise a way to trigger the effective intrinsic repair of AC. However, adoption of antler cartilage model for AC repair requires the demonstration that the cartilage specific signalling pathways also prevail in antler chondrogenesis. To achieve this, in the present study we silenced expression of Cbfa1, a key factor regulatingendochondral ossification, using RNAi, and showed that expression of the downstream genes type I collagen and osteocalcin were suppressed which, in turn, inhibited endochondral ossification process taking place in the antler stem cell-formed nodules. Therefore, we provided further evidence at molecular level that antler could be developed as novel model for the study of AC repair. The eventual identification of the extrinsic factors dictating the phenotype switch between the vascular and avascular state of antler cartilage will open up a new avenue for the cure of osteoarthritis. © 2012 Sun et al.


Yang F.,Chinese Academy of Agricultural Sciences | Yang F.,State Key Laboratory for Molecular Biology of Special Economic Animals | Gao X.,Chinese Academy of Agricultural Sciences | Gao X.,State Key Laboratory for Molecular Biology of Special Economic Animals | And 2 more authors.
Animal Production Science | Year: 2012

The purpose of this study was to investigate the influence of dietary protein levels on the performance of sika deer. Twenty-four male sika deer were randomly assigned into three treatments, where they were fed a diet containing either 12, 16 or 20% crude protein (CP). During the antler growth period the average bodyweight gain in 12, 16 and 20% CP levels was 17.3, 19.9 and 14.4 kg, respectively; antler yield was 2224, 2518 and 2246 g, respectively. A significant positive relationship (P 0.01) was found between serum insulin-like growth factor (IGF)-I concentration and bodyweight gain (P 0.01) and antler yield (P 0.01), using the regression equations: bodyweight gain (kg) = 0.06IGF-1 (ng/mL) 52.14 (R2 = 0.69, n = 8) and antler yield (g) = 3.55IGF-1 (ng/mL) 1659.4 (R2 = 0.77, n = 8), respectively. We concluded that 16% dietary protein was optimal for bodyweight gain and antler yield during the antler growth period in the sika deer. © 2012 CSIRO.


Ba H.,Chinese Academy of Agricultural Sciences | Ba H.,State Key Laboratory for Molecular Biology of Special Economic Animals | Wang D.,Chinese Academy of Agricultural Sciences | Wang D.,State Key Laboratory for Molecular Biology of Special Economic Animals | And 2 more authors.
Molecular Genetics and Genomics | Year: 2016

MicroRNAs (miRNAs) can effectively regulate gene expression at the post-transcriptional level and play a critical role in tissue growth, development and regeneration. Our previous studies showed that antler regeneration is a stem cell-based process and antler stem cells reside in the periosteum of a pedicle, the permanent bony protuberance, from which antler regeneration takes place. Antlers are the only mammalian organ that can fully regenerate and hence provide a unique opportunity to identify miRNAs that are involved in organ regeneration. In the present study, we used next generation sequencing technology sequenced miRNAs of the stem cells derived from either the potentiated or the dormant pedicle periosteum. A population of both conserved and 20 deer-specific miRNAs was identified. These conserved miRNAs were derived from 453 homologous hairpin precursors across 88 animal species, and were further grouped into 167 miRNA families. Among them, the miR-296 is embryonic stem cell-specific. The potentiation process resulted in the significant regulation (>±2 Fold, q value <0.05) of conserved miRNAs; 8 miRNA transcripts were down- and 6 up-regulated. Several GO biology processes and the Wnt, MAPK and TGF-beta signaling pathways were found to be up-regulated as part of antlerogenic stem cell potentiation process. This research has identified miRNAs that are associated either with the dormant or the potentiated antler stem cells and identified some target miRNAs for further research into their role played in mammalian organ regeneration. © 2016 Springer-Verlag Berlin Heidelberg

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