The present review aims to illustrate the strategies that are being implemented to regenerate or bioengineer livers for clinical purposes.There are two general pathways to liver bioengineering and regeneration.The fir...The present review aims to illustrate the strategies that are being implemented to regenerate or bioengineer livers for clinical purposes.There are two general pathways to liver bioengineering and regeneration.The first consists of creating a supporting scaffold,either synthetically or by decellularization of human or animal organs,and seeding cells on the scaffold,where they will mature either in bioreactors or in vivo.This strategy seems to offer the quickest route to clinical translation,as demonstrated by the development of liver organoids from rodent livers which were repopulated with organ specific cells of animal and/or human origin.Liver bioengineering has potential for transplantation and for toxicity testing during preclinical drug development.The second possibility is to induce liver regeneration of dead or resected tissue by manipulating cell pathways.In fact,it is well known that the liver has peculiar regenerative potential which allows hepatocyte hyperplasia after amputation of liver volume.Infusion of autologous bone marrow cells,which aids in liver regeneration,into patients was shown to be safe and to improve their clinical condition,but the specific cells responsible for liver regeneration have not yet been determined and the underlying mechanisms remain largely unknown.A complete understanding of the cell pathways and dynamics and of the functioning of liver stem cell niche is necessary for the clinical translation of regenerative medicine strategies.As well,it will be crucial to elucidate the mechanisms through which cells interact with the extracellular matrix,and how this latter supports and drives cell fate.展开更多
Extant giant pandas are divided into Sichuan and Qinling subspecies.The giant panda has many speciesspecific characteristics,including comparatively small organs for body size,small genitalia of male individuals,and l...Extant giant pandas are divided into Sichuan and Qinling subspecies.The giant panda has many speciesspecific characteristics,including comparatively small organs for body size,small genitalia of male individuals,and low reproduction.Here,we report the most contiguous,high-quality chromosomelevel genomes of two extant giant panda subspecies to date,with the first genome assembly of the Qinling subspecies.Compared with the previously assembled giant panda genomes based on short reads,our two assembled genomes increased contiguity over 200-fold at the contig level.Additional sequencing of 25 individuals dated the divergence of the Sichuan and Qinling subspecies into two distinct clusters from 10,000 to 12,000 years ago.Comparative genomic analyses identified the loss of regulatory elements in the dachshund family transcription factor 2(DACH2)gene and specific changes in the synaptotagmin 6(SYT6)gene,which may be responsible for the reduced fertility of the giant panda.Positive selection analysis between the two subspecies indicated that the reproduction-associated IQ motif containing D(IQCD)gene may at least partly explain the different reproduction rates of the two subspecies.Furthermore,several genes in the Hippo pathway exhibited signs of rapid evolution with giant panda-specific variants and divergent regulatory elements,which may contribute to the reduced inner organ sizes of the giant panda.展开更多
文摘The present review aims to illustrate the strategies that are being implemented to regenerate or bioengineer livers for clinical purposes.There are two general pathways to liver bioengineering and regeneration.The first consists of creating a supporting scaffold,either synthetically or by decellularization of human or animal organs,and seeding cells on the scaffold,where they will mature either in bioreactors or in vivo.This strategy seems to offer the quickest route to clinical translation,as demonstrated by the development of liver organoids from rodent livers which were repopulated with organ specific cells of animal and/or human origin.Liver bioengineering has potential for transplantation and for toxicity testing during preclinical drug development.The second possibility is to induce liver regeneration of dead or resected tissue by manipulating cell pathways.In fact,it is well known that the liver has peculiar regenerative potential which allows hepatocyte hyperplasia after amputation of liver volume.Infusion of autologous bone marrow cells,which aids in liver regeneration,into patients was shown to be safe and to improve their clinical condition,but the specific cells responsible for liver regeneration have not yet been determined and the underlying mechanisms remain largely unknown.A complete understanding of the cell pathways and dynamics and of the functioning of liver stem cell niche is necessary for the clinical translation of regenerative medicine strategies.As well,it will be crucial to elucidate the mechanisms through which cells interact with the extracellular matrix,and how this latter supports and drives cell fate.
基金supported by the National Key Program(2016YFC0503200)from the Ministry of Science and Technology of Chinaa special grant for the giant panda from the State Forestry Administration of the People’s Republic of China+2 种基金the Fundamental Research Funds for the Central Universities of the People’s Republic of Chinathe Foundation of Key Laboratory of State Forestry and Grassland Administration(State Park Administration)on Conservation Biology of Rare Animals in the Giant Panda National Park(KLSFGAGP2020.002)the Guangdong Provincial Key Laboratory of Genome Read and Write(2017B030301011)。
文摘Extant giant pandas are divided into Sichuan and Qinling subspecies.The giant panda has many speciesspecific characteristics,including comparatively small organs for body size,small genitalia of male individuals,and low reproduction.Here,we report the most contiguous,high-quality chromosomelevel genomes of two extant giant panda subspecies to date,with the first genome assembly of the Qinling subspecies.Compared with the previously assembled giant panda genomes based on short reads,our two assembled genomes increased contiguity over 200-fold at the contig level.Additional sequencing of 25 individuals dated the divergence of the Sichuan and Qinling subspecies into two distinct clusters from 10,000 to 12,000 years ago.Comparative genomic analyses identified the loss of regulatory elements in the dachshund family transcription factor 2(DACH2)gene and specific changes in the synaptotagmin 6(SYT6)gene,which may be responsible for the reduced fertility of the giant panda.Positive selection analysis between the two subspecies indicated that the reproduction-associated IQ motif containing D(IQCD)gene may at least partly explain the different reproduction rates of the two subspecies.Furthermore,several genes in the Hippo pathway exhibited signs of rapid evolution with giant panda-specific variants and divergent regulatory elements,which may contribute to the reduced inner organ sizes of the giant panda.
