Revolutionize livestock breeding in the future: an animal embryo-stem cell breeding system in a dish

Meat and milk production needs to increase ～ 70–80% relative to its current levels for satisfying the human needs in 2050.However,it is impossible to achieve such genetic gain by conventional animal breeding systems.Based on recent advances with regard to in vitro induction of germ cell from pluripotent stem cells,herein we propose a novel embryo-stem cell breeding system.Distinct from the conventional breeding system in farm animals that involves selecting and mating individuals,the novel breeding system completes breeding cycles from parental to offspring embryos directly by selecting and mating embryos in a dish.In comparison to the conventional dairy breeding scheme,this system can rapidly achieve 30–40 times more genetic gain by significantly shortening generation interval and enhancing selection intensity.However,several major obstacles must be overcome before we can fully use this system in livestock breeding,which include derivation and mantaince of pluripotent stem cells in domestic animals,as well as in vitro induction of primordial germ cells,and subsequent haploid gametes.Thus,we also discuss the potential efforts needed in solving the obstacles for application this novel system,and elaborate on their groundbreaking potential in livestock breeding.This novel system would provide a revolutionary animal breeding system by offering an unprecedented opportunity for meeting the fast-growing meat and milk demand of humans.

Construction Technology of Pipe Jacking Method through Underground Obstacles

Due to the increase in the global urban population and the continuous improvement of requirements,urban in­frastructure construction is developing rapidly.Various underground pipelines and channels are increasing and the demand is increasing.As a trenchless technology,pipe jacking construction technology has been widely used in pipeline laying and underpass construction,especially in complex urban environments and cross-river regions,which has great advantages[1].

Overcoming barriers to the clinical utilization of iPSCs:reprogramming efficiency,safety and quality

Differentiated cells can be reprogrammed into pluripotent stem cells,known as“induced pluripotent stem cells”(iPSCs),through the overexpression of defined transcription factors.The creation of iPSC lines has opened new avenues for patient-specific cell replacement therapies for regenerative medicine.However,the clinical utilization of iPSCs is largely impeded by two limitations.The first limitation is the low efficiency of iPSCs generation from differentiated cells.The second limitation is that many iPSC lines are not authentically pluripotent,as many cell lines inefficiently differentiate into differentiated cell types when they are tested for their ability to complement embryonic development.Thus,the“quality”of iPSCs must be increased if they are to be differentiated into specialized cell types for cell replacement therapies.Overcoming these two limitations is paramount to facilitate the widespread employment of iPSCs for therapeutic purposes.Here,we summarize recent progress made in strategies enabling the efficient production of high-quality iPSCs,including choice of reprogramming factors,choice of target cell type,and strategies to improve iPSC quality.

Novel pipe-roof method for a super shallow buried and large-span metro underground station

To address the inadequacies of traditional pipe-roof methods,the steel support cutting pipe method(SSCP)—a novel pipe-roof method that improves construction security and underground space usage—is proposed.To further explore the applications of SSCP,its design scheme ought to be optimized.The failure mode and mechanical behaviors of the SSCP were investigated through laboratory experiments.Subsequently,a series of finite element models(FEMs)was established to study the deformation characteristics.Further,the parameters of the steel support of the proposed structure were optimized using fuzzy mathematics.The results indicated the ultimate bearing capacity to be 366.8 kN,and the specimen began to yield when the external load reached 70%of the ultimate value.The lon-gitudinal spacing of the steel supports,transverse steel support size,and vertical steel support size had significant effect on the vertical deformation of the steel support and the ground settlement.Finally,the optimal combination of steel supports for the SSCP structure was obtained.

Porcine pluripotent stem cells: progress, challenges and prospects

Pluripotent stem cells(PSCs) are characterized by their capacity for high self-renewal and multiple differentiation potential and include embryonic stem cells, embryonic germ cells and induced PSCs. PSCs provide a very suitable model for the studies of human diseases, drugs screening, regenerative medicine and developmental biology research. Pigs are considered as an ideal model for preclinical development of human xenotransplantation, therapeutic approaches and regenerative medicine because of their size and physiological similarity to humans. However, lack of knowledge about the derivation, characterization and pluripotency mechanisms of porcine PSCs hinders progress in these biotechnologies. In this review, we discuss the latest progress on porcine PSCs generation, evaluation criteria for pluripotency, the scienti?c and technical questions arising from these studies. We also introduce our perspectives on porcine PSC research, in the hope of providing new ideas for generating naive porcine PSCs and animal breeding.

Progress,problems and prospects of porcine pluripotent stem cells

Pluripotent stem cells(PSCs),including embryonic stem cells(ESCs)and induced PSCs(iPSCs),can differentiate into cells of the three germ layers,suggesting that PSCs have great potential for basic developmental biology research and wide applications for clinical medicine.Genuine ESCs and iPSCs have been derived from mice and rats,but not from livestock such as the pig-an ideal animal model for studying human disease and regenerative medicine due to similarities with human physiologic processes.Efforts to derive porcine ESCs and iPSCs have not yielded high-quality PSCs that can produce chimeras with germline transmission.Thus,exploration of the unique porcine gene regulation network of preimplantation embryonic development may permit optimization of in vitro culture systems for raising porcine PSCs.Here we summarize the recent progress in porcine PSC generation as well as the problems encountered during this progress and we depict prospects for generating porcine naive PSCs.

Pluripotent stem cells secrete Activin A to improve their epiblast competency after injection into recipient embryos

It is not fully clear why there is a higher contribution of pluripotent stem cells （PSCs） to the chimera produced by injection of PSCs into 4-cell or 8-cell stage embryos compared with blastocyst injection. Here, we show that not only embryonic stem cells （ESCs） but also induced pluripotent stem cells （iPSCs） can generate F0 nearly 100% donor cell-derived mice by 4-cell stage embryo injection, and the approach has a ＂dose effect＂. Through an analysis of the PSC-secreted proteins, Activin A was found to impede epiblast （EPI） lineage development while promoting trophectoderm （TE） differentiation, resulting in replacement of the EPI lineage of host embryos with PSCs. Interestingly, the injection of ESCs into blastocysts cultured with Activin A （cultured from 4-cell stage to early blastocyst at E3.5） could increase the contribution of ESCs to the chimera. The results indicated that PSCs secrete protein Activin A to improvetheir EPI competency after injection into recipient embryos through influencing the development of mouse early embryos. This result is useful for optimizing the chimera production system and for a deep understand- ing of PSCs effects on early embryo development.

Testing the polar auxin transport model with a selective plasma membrane H^(+)-ATPase inhibitor

Auxin is unique among plant hormones in that its function requires polarized transport across plant cells.A chemiosmotic model was proposed to explain how polar auxin transport is derived by the H^(+)gradient across the plasma membrane(PM)established by PM H^(+)-adenosine triphosphatases(ATPases).However,a classical genetic approach by mutations in PM H^(+)-ATPase members did not result in the ablation of polar auxin distribution,possibly due to functional redundancy in this gene family.To confirm the crucial role of PM H^(+)-ATPases in the polar auxin transport model,we employed a chemical genetic approach.Through a chemical screen,we identified protonstatin-1(PS-1),a selective small-molecule inhibitor of PM H^(+)-ATPase activity that inhibits auxin transport.Assays with transgenic plants and yeast strains showed that the activity of PM H^(+)-ATPases affects auxin uptake as well as acropetal and basipetal polar auxin transport.We propose that PS-1 can be used as a tool to interrogate the function of PM H^(+)-ATPases.Our results support the chemiosmotic model in which PM H^(+)-ATPase itself plays a fundamental role in polar auxin transport.

Highly efficient generation of biallelic reporter gene knock-in mice via CRISPR-mediated genome editing of ESCs

Dear Editor,Targeted gene knock-out and knock-in mice are valuable tools for elucidating the function of genes in vivo （Capecchi, 2001）. Recently, the Cas9 endonuclease from Streptococcus pyogenes type Ⅱ CRISPR system has been demonstrated as a powerful tool for gene targeting.

Highlights for special issue on “Large Animal Stem Cells”

Biological techniques such as stem cell culture, somatic cell reprogramming and gene editing are important for the large animal breeding. Also, these techniques can produce large animal models, which hold great potential for developing disease treatment and clinical applications.