Mouse and human somatic cells can be induced to become pluripotent stem （iPS） cells by retroviral transduction with defined transcription factors . Reprogrammed pluripotent stem cells have great potential for regene...Mouse and human somatic cells can be induced to become pluripotent stem （iPS） cells by retroviral transduction with defined transcription factors . Reprogrammed pluripotent stem cells have great potential for regenerative medicine and also provide a good experi- mental system for studying epigenetic reprogramming and differentiation. However, at present, the reprogram- ming process is still somewhat slow and ineffective.展开更多
The spontaneous oscillatory contraction（SPOC） of myofibrils is the essential property inherent to the contractile system of muscle. Muscle contraction results from cyclic interactions between actin filament and myos...The spontaneous oscillatory contraction（SPOC） of myofibrils is the essential property inherent to the contractile system of muscle. Muscle contraction results from cyclic interactions between actin filament and myosin II which is a dimeric motor protein with two heads. Taking the two heads of myosin II as an indivisible element and considering the effects of cooperative behavior between the two heads on rate constants in the mechanochemical cycle, the present work proposes the tenstate mechanochemical cycle model for myosin II dimer. The simulations of this model show that the proportion of myosin II in different states periodically changes with time, which results in the sustained oscillations of contractive tension, and serves as the primary factor for SPOC. The good fit of this model to experimental results suggests that the cooperative interaction between the two heads of myosin II dimer may be one of the underlying mechanisms for muscle contraction.展开更多
The generation and propagation characteristics of bright spatial bound-soliton pairs (BSPs) are investigated under the diffusion effect in photovoltaic photorefractive crystals by numerical simulation. The results sho...The generation and propagation characteristics of bright spatial bound-soliton pairs (BSPs) are investigated under the diffusion effect in photovoltaic photorefractive crystals by numerical simulation. The results show that two coherent solitons, one as the signal light and the other as the control light, can form a BSP when the peak intensity of the control light is appropriately selected. Moreover, under the diffusion effect, the BSP experiences a self-bending process during propagating and the center of the BSP moves on a parabolic trajectory. Furthermore, the lateral shift of the BSP at the output face of the crystal can be manipulated by adjusting the peak intensity of the control light. The research results provide a method for the design of all-optical switching and routing based on the manipulation of the lateral position of BSPs.展开更多
The pluripotent state between human and mouse embryonic stem cells is different.Pluripotent state of human embryonic stem cells(ESCs)is believed to be primed and is similar with that of mouse epiblast stem cells(EpiSC...The pluripotent state between human and mouse embryonic stem cells is different.Pluripotent state of human embryonic stem cells(ESCs)is believed to be primed and is similar with that of mouse epiblast stem cells(EpiSCs),which is different from the naïve state of mouse ESCs.Human ESCs could be converted into a naïve state through exogenous expression of defined transcription factors(Hanna et al.,2010).Here we report a rapid conversion of human ESCs to mouse ESC-like naïve states only by modifying the culture conditions.These converted human ESCs,which we called mhESCs(mouse ESC-like human ESCs),have normal karyotype,allow single cell passage,exhibit domed morphology like mouse ESCs and express some pluripotent markers similar with mouse ESCs.Thus the rapid conversion established a naïve pluripotency in human ESCs like mouse ESCs,and provided a new model to study the regulation of pluripotency.展开更多
Mouse embryonic stem cells(mESCs)derived from inner cell mass(ICM)of pre-implantation embryos,can maintain undifferentiated state when cultured in N2B27 medium supplemented with GSK3inhibitor CHIR99021 and MEK inhibit...Mouse embryonic stem cells(mESCs)derived from inner cell mass(ICM)of pre-implantation embryos,can maintain undifferentiated state when cultured in N2B27 medium supplemented with GSK3inhibitor CHIR99021 and MEK inhibitor PD0325901(‘‘2i’’)and leukemia inhibitor factor(LIF).Compare to conventional culture medium,all components of this medium are defined.With the N2B27 medium,‘‘2i’’and LIF,mESCs can contribute to the germline of the chimeric embryos,however,whether the‘‘all-ES cells’’mice can been generated by tetraploid complementation is unclear yet,while the tetraploid complementation serve as a golden standard to assess the pluripotency of ES cells.Here,our study showed that mESCs derived and cultured with the N2B27 complete medium could generate fertile mice by tetraploid complementation.In addition,the survival rate of tetraploid complementation mice produced by inbred mES cell lines is higher than the conventional culture condition,and increased the percentage of Oct4 positive cells contrast to conventional medium either.Therefore,the N2B27 medium supplemented with‘‘2i’’and LIF is an alternative choice forthe derivation and long-term culture of mouse embryonic stem cells.展开更多
Cavitation within the tip vortex(TV)flow remains a challenging issue in the design of high-speed and low-noise hydraulic machinery.In this paper,the TV cavitating flow around an elliptical hydrofoil is calculated by u...Cavitation within the tip vortex(TV)flow remains a challenging issue in the design of high-speed and low-noise hydraulic machinery.In this paper,the TV cavitating flow around an elliptical hydrofoil is calculated by using large eddy simulation(LES)combined with a modified Schnerr-Sauer(S-S)cavitation model.The original S-S cavitation model is modified by taking into account the typical effect of vortex flow.The partial pressure term which can describe the vortex quantitatively and qualitatively is confirmed asρ_(m)ω^(2) x r _(c)^(2) ,and is considered into the R-P equation of the modified S-S cavitation model.Comparison between the numerical and experimental results shows good agreement in the form and evolution of cavities,including attached cavities(AC)and tip vortex cavities(TVC).The vorticity transport equation is utilized to investigate the dynamic mechanisms of the vortex development around the TVC.Further analyses indicate that cavitation in the TV flow influences the pressure in the core of the cavity and the local flow patterns.Typical vortex structures in the TV cavitating flow include TV,secondary vortex(SV)and wake vortex(WV).The direction and magnitude of the rotation effect can be described by axial vorticity which is drawn on the iso-surface of Q=1×105 s−2.The development of the TV cavitating flow can be divided into two stages:Stage I,the development and fusion of TV,SV,stage II,the dissipation of SV.The stretching term dominates the evolution of TV,and the dilatation term is the main reason in the mergence process of SV.展开更多
In all the connexin-associated human diseases, deafness is one of the most important diseases with high frequency. The mu- tations of GJB2 （gap junction protein β2, also called connexin 26, Cx26） gene link with non...In all the connexin-associated human diseases, deafness is one of the most important diseases with high frequency. The mu- tations of GJB2 （gap junction protein β2, also called connexin 26, Cx26） gene link with nonsyndromic or syndromic senso- rineural hearing loss and were shown to account for a large proportion of congenital deaf cases in many studied populations （del Castillo and del Castillo, 2011）. For example, the 235de1C mutation in GJB2 shows the frequency of approximately 1% and is the most frequent mutation in East Asian population （Yan et al., 2003）. Many efforts have been put to study the function of Gjb2 gene in both mouse model and human. In mouse, extensive deletion of Gjb2 causes embryo lethal due to the decreased transplacental glucose uptake, which was not found in human （Takata and Hirano, 1997; Gabriel et al., 1998）. In human, GJB2 deficiency is not able to cause embryo lethal （D＇Andrea et al., 2002）. However, the study of GJB2-associated hearing loss is hampered by many difficulties, such as unobtainable human cochlea and acoustic nerve tissues, and therefore the GJB2-associated hearing loss are underlying mechanisms of still remaining unclear.展开更多
Induced pluripotent stem （iPS） cells can be generated by forced expression of four pluripotency factors in somatic cells. This has received much attention in recent years since it may offer us a promising donor cell...Induced pluripotent stem （iPS） cells can be generated by forced expression of four pluripotency factors in somatic cells. This has received much attention in recent years since it may offer us a promising donor cell source for cell transplantation therapy. There has been great progress in iPS cell research in the past few years. However, several issues need to be further addressed in the near future before the clinical application of iPS cells, like the immunogenieity of iPS cells, the variability of differentiation potential and most importantly tumor formation of the iPS derivative cells. Here, we review recent progress in research into the pluripotency of iPS cells.展开更多
Haploid pluripotent stem cells,such as haploid embryonic stem cells(haESCs),facilitate the genetic study of recessive traits.In vitro,fish haESCs maintain haploidy in both undifferentiated and differentiated states,bu...Haploid pluripotent stem cells,such as haploid embryonic stem cells(haESCs),facilitate the genetic study of recessive traits.In vitro,fish haESCs maintain haploidy in both undifferentiated and differentiated states,but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested.Here,wereport thatmousehaESCs can differentiate in vitro into haploid epiblast stem cells(haEpiSCs),which maintain an intact haploid genome,unlimited self-renewal potential,and durable pluripotency to differentiate into various tissues in vitro and in vivo.Mechanistically,the maintenance of self-renewal potential depends on the Activin/bFGF pathway.We further show that haEpiSCs can differentiate in vitro into haploid progenitor-like cells.When injected into the cytoplasm of an oocyte,androgenetic haEpiSC(ahaEpiSCs)can support embryonic development until midgestation(E12.5).Together,these resultsdemonstrate durable pluripotency inmousehaESCs andhaEpiSCs,aswell asthe valuable potential of using these haploid pluripotent stem cells in high-throughput genetic screening.展开更多
Spermatogonial stem cells （SSCs） reside on the basement membrane of the seminiferous tubules in mammalian testes （Nagano et al., 1998）. After isolation and purification of SSCs from mouse testis, SSCs can be cultu...Spermatogonial stem cells （SSCs） reside on the basement membrane of the seminiferous tubules in mammalian testes （Nagano et al., 1998）. After isolation and purification of SSCs from mouse testis, SSCs can be cultured in vitro to derive germ-line stem cells （GSCs） which have the ability of proliferation over 2 years （Kanatsu-Shinohara et al.. 2003;展开更多
The laboratory rat was one of the earliest mammalian species for scientific research and used as animal disease models in physiology, toxicology, behavior, immunology, and tumor-biology for over 150 years （Jacob, 199...The laboratory rat was one of the earliest mammalian species for scientific research and used as animal disease models in physiology, toxicology, behavior, immunology, and tumor-biology for over 150 years （Jacob, 1999）. However, rat lags far behind mouse in generating human disease models and functional genomic studies because of the lack of authentic rat embryonic stem （ES） cells （Voigt and Serikawa, 2009）,展开更多
Although somatic cells can be reprogrammed to pluripotent stem cells(PsCs)with pure chemicals,authentic pluripotency of chemically induced pluripotent stem celis(CipsCs)has never been achieved through tetraploid compl...Although somatic cells can be reprogrammed to pluripotent stem cells(PsCs)with pure chemicals,authentic pluripotency of chemically induced pluripotent stem celis(CipsCs)has never been achieved through tetraploid complementation assay.Spontaneous reprogramming of spermatogonial stem cells(ssCs)was another non-transgenic way to obtain PsCs,but this process lacks mechanistic explanation.Here,we reconstructed the trajectory of mouse SsC reprogramming and developed a five-chemical combination,boosting the reprogramming effciency by nearly 80-to 100-folds.More importantly,chemical induced germline-derived PsCs(5C-gPSCs),but not gpsCs and chemical induced pluripotent stem cells,had authentic pluripotency,as determined by tetraploid complementation.Mechanistically,ssCs traversed through an inverted pathway of in vivo germ ceil development,exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts.Besides,ssC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5c-gPsCs,which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles.Our work sheds ight on the unique regulatory network underpinning SsC reprogramming,providing insights to understand generic mechanisms for cell-fate decision and epigenetic-relateddisorders in regenerative medicine.展开更多
基金These three authors contributed equally to this work. This study was supported in part by grants from the Hi-Tech Research and Development Program of China （2006AA02A101 to QZ）, the National Natural Science Foundation of China （30670229 to QZ）, China National Basic Research Program （2006CB701500, 2007CB947700 and 2007CB947800）, the Shanghai Leading Academic Discipline Project （$30201）, and STCSM Project （08dj 1400502）.
文摘Mouse and human somatic cells can be induced to become pluripotent stem （iPS） cells by retroviral transduction with defined transcription factors . Reprogrammed pluripotent stem cells have great potential for regenerative medicine and also provide a good experi- mental system for studying epigenetic reprogramming and differentiation. However, at present, the reprogram- ming process is still somewhat slow and ineffective.
基金Project supported by Research Program of Science and Technology at Universities of Inner Mongolia Autonomous Region,China(Grant Nos.NJZY16493and NJZC17458)
文摘The spontaneous oscillatory contraction（SPOC） of myofibrils is the essential property inherent to the contractile system of muscle. Muscle contraction results from cyclic interactions between actin filament and myosin II which is a dimeric motor protein with two heads. Taking the two heads of myosin II as an indivisible element and considering the effects of cooperative behavior between the two heads on rate constants in the mechanochemical cycle, the present work proposes the tenstate mechanochemical cycle model for myosin II dimer. The simulations of this model show that the proportion of myosin II in different states periodically changes with time, which results in the sustained oscillations of contractive tension, and serves as the primary factor for SPOC. The good fit of this model to experimental results suggests that the cooperative interaction between the two heads of myosin II dimer may be one of the underlying mechanisms for muscle contraction.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 61875058, 11874018, 11974006, and 61378036).
文摘The generation and propagation characteristics of bright spatial bound-soliton pairs (BSPs) are investigated under the diffusion effect in photovoltaic photorefractive crystals by numerical simulation. The results show that two coherent solitons, one as the signal light and the other as the control light, can form a BSP when the peak intensity of the control light is appropriately selected. Moreover, under the diffusion effect, the BSP experiences a self-bending process during propagating and the center of the BSP moves on a parabolic trajectory. Furthermore, the lateral shift of the BSP at the output face of the crystal can be manipulated by adjusting the peak intensity of the control light. The research results provide a method for the design of all-optical switching and routing based on the manipulation of the lateral position of BSPs.
基金by grants from the China National Basic Research Program(Grant No.2011CB965300)to L.W.grants from the National Natural Science Foundation of China(Grant No.90919060)to Q.Z.grants from the"Strategic Priority Research Program"of the Chinese Academy of Sciences(No.XDA01020101)to Q.Z.
文摘The pluripotent state between human and mouse embryonic stem cells is different.Pluripotent state of human embryonic stem cells(ESCs)is believed to be primed and is similar with that of mouse epiblast stem cells(EpiSCs),which is different from the naïve state of mouse ESCs.Human ESCs could be converted into a naïve state through exogenous expression of defined transcription factors(Hanna et al.,2010).Here we report a rapid conversion of human ESCs to mouse ESC-like naïve states only by modifying the culture conditions.These converted human ESCs,which we called mhESCs(mouse ESC-like human ESCs),have normal karyotype,allow single cell passage,exhibit domed morphology like mouse ESCs and express some pluripotent markers similar with mouse ESCs.Thus the rapid conversion established a naïve pluripotency in human ESCs like mouse ESCs,and provided a new model to study the regulation of pluripotency.
基金supported by the National Basic Research Program of China(2012CBA01300 and2012CB966500)
文摘Mouse embryonic stem cells(mESCs)derived from inner cell mass(ICM)of pre-implantation embryos,can maintain undifferentiated state when cultured in N2B27 medium supplemented with GSK3inhibitor CHIR99021 and MEK inhibitor PD0325901(‘‘2i’’)and leukemia inhibitor factor(LIF).Compare to conventional culture medium,all components of this medium are defined.With the N2B27 medium,‘‘2i’’and LIF,mESCs can contribute to the germline of the chimeric embryos,however,whether the‘‘all-ES cells’’mice can been generated by tetraploid complementation is unclear yet,while the tetraploid complementation serve as a golden standard to assess the pluripotency of ES cells.Here,our study showed that mESCs derived and cultured with the N2B27 complete medium could generate fertile mice by tetraploid complementation.In addition,the survival rate of tetraploid complementation mice produced by inbred mES cell lines is higher than the conventional culture condition,and increased the percentage of Oct4 positive cells contrast to conventional medium either.Therefore,the N2B27 medium supplemented with‘‘2i’’and LIF is an alternative choice forthe derivation and long-term culture of mouse embryonic stem cells.
基金supported by the National Natural Science Foundation of China(Grant No.52009001)supported by the Postdoctoral Research Foundation of China(Granr No.2020M680380)+1 种基金the Natural Science Foundation Projectof Chongqing,Chongqing Science and Technology Commission(Grant No.cstc2021jcyj-msxmX1046)the Beijing Institute of Technology Research Fund Program for Young Scholars(Grant No.XSQD-202003008).
文摘Cavitation within the tip vortex(TV)flow remains a challenging issue in the design of high-speed and low-noise hydraulic machinery.In this paper,the TV cavitating flow around an elliptical hydrofoil is calculated by using large eddy simulation(LES)combined with a modified Schnerr-Sauer(S-S)cavitation model.The original S-S cavitation model is modified by taking into account the typical effect of vortex flow.The partial pressure term which can describe the vortex quantitatively and qualitatively is confirmed asρ_(m)ω^(2) x r _(c)^(2) ,and is considered into the R-P equation of the modified S-S cavitation model.Comparison between the numerical and experimental results shows good agreement in the form and evolution of cavities,including attached cavities(AC)and tip vortex cavities(TVC).The vorticity transport equation is utilized to investigate the dynamic mechanisms of the vortex development around the TVC.Further analyses indicate that cavitation in the TV flow influences the pressure in the core of the cavity and the local flow patterns.Typical vortex structures in the TV cavitating flow include TV,secondary vortex(SV)and wake vortex(WV).The direction and magnitude of the rotation effect can be described by axial vorticity which is drawn on the iso-surface of Q=1×105 s−2.The development of the TV cavitating flow can be divided into two stages:Stage I,the development and fusion of TV,SV,stage II,the dissipation of SV.The stretching term dominates the evolution of TV,and the dilatation term is the main reason in the mergence process of SV.
基金supported by grants from the National Key Basic Research Programs of China (Nos. 2012CB966600 and 2012CB967900)the National Natural Science Foundation Project (No. 31371506)the 12th Five-Year National Key Technologies R&D Program (No. 2012BAI12B00)
文摘In all the connexin-associated human diseases, deafness is one of the most important diseases with high frequency. The mu- tations of GJB2 （gap junction protein β2, also called connexin 26, Cx26） gene link with nonsyndromic or syndromic senso- rineural hearing loss and were shown to account for a large proportion of congenital deaf cases in many studied populations （del Castillo and del Castillo, 2011）. For example, the 235de1C mutation in GJB2 shows the frequency of approximately 1% and is the most frequent mutation in East Asian population （Yan et al., 2003）. Many efforts have been put to study the function of Gjb2 gene in both mouse model and human. In mouse, extensive deletion of Gjb2 causes embryo lethal due to the decreased transplacental glucose uptake, which was not found in human （Takata and Hirano, 1997; Gabriel et al., 1998）. In human, GJB2 deficiency is not able to cause embryo lethal （D＇Andrea et al., 2002）. However, the study of GJB2-associated hearing loss is hampered by many difficulties, such as unobtainable human cochlea and acoustic nerve tissues, and therefore the GJB2-associated hearing loss are underlying mechanisms of still remaining unclear.
基金supported by grants from the National Basic Research Program of China(Grant No.2012CBA01300 and 2012CB966500)
文摘Induced pluripotent stem （iPS） cells can be generated by forced expression of four pluripotency factors in somatic cells. This has received much attention in recent years since it may offer us a promising donor cell source for cell transplantation therapy. There has been great progress in iPS cell research in the past few years. However, several issues need to be further addressed in the near future before the clinical application of iPS cells, like the immunogenieity of iPS cells, the variability of differentiation potential and most importantly tumor formation of the iPS derivative cells. Here, we review recent progress in research into the pluripotency of iPS cells.
基金supported by grants from the National Basic Research Program of China(2012CBA01300 to Q.Z.and 2014CB964800 to W.L.)the National Science Foundation of China(91319308 to Q.Z.).
文摘Haploid pluripotent stem cells,such as haploid embryonic stem cells(haESCs),facilitate the genetic study of recessive traits.In vitro,fish haESCs maintain haploidy in both undifferentiated and differentiated states,but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested.Here,wereport thatmousehaESCs can differentiate in vitro into haploid epiblast stem cells(haEpiSCs),which maintain an intact haploid genome,unlimited self-renewal potential,and durable pluripotency to differentiate into various tissues in vitro and in vivo.Mechanistically,the maintenance of self-renewal potential depends on the Activin/bFGF pathway.We further show that haEpiSCs can differentiate in vitro into haploid progenitor-like cells.When injected into the cytoplasm of an oocyte,androgenetic haEpiSC(ahaEpiSCs)can support embryonic development until midgestation(E12.5).Together,these resultsdemonstrate durable pluripotency inmousehaESCs andhaEpiSCs,aswell asthe valuable potential of using these haploid pluripotent stem cells in high-throughput genetic screening.
基金supported by the National Basic Research Program of China(No.2013CB947903)the National Natural Science Foundation Project Outstanding Young Scholars(No.31322036)
文摘Spermatogonial stem cells （SSCs） reside on the basement membrane of the seminiferous tubules in mammalian testes （Nagano et al., 1998）. After isolation and purification of SSCs from mouse testis, SSCs can be cultured in vitro to derive germ-line stem cells （GSCs） which have the ability of proliferation over 2 years （Kanatsu-Shinohara et al.. 2003;
基金supported by the grants from the China National Basic Research Program(No.2012CB966501) to X.Zthe National High Technology R&D Program of China (No.2011AA020108) to Q.Z.the "Strategic Priority Research Program" of the Chinese Academy of Sciences(No. XDA01030101)
文摘The laboratory rat was one of the earliest mammalian species for scientific research and used as animal disease models in physiology, toxicology, behavior, immunology, and tumor-biology for over 150 years （Jacob, 1999）. However, rat lags far behind mouse in generating human disease models and functional genomic studies because of the lack of authentic rat embryonic stem （ES） cells （Voigt and Serikawa, 2009）,
基金supported by grants from the National Key R&D Program of China(2020YFA0113300 to M.W.,2018YFA0107601 to F.T.,2019YFA0801802 to M.W.,2022YFA0806300 to X.-Y.Z.)the National Natural Science Foundation of China(82071711 to X.-Y.Z.,32170866 to M.W.,U22A20278 to X.-Y.Z.)+2 种基金Key Research&Development Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)(2018GZR110104002 to X.-Y.Z.)Guangdong Basic and Applied Basic Research Foundation(2021A1515010802 to M.W.)National Demonstration Center for Experimental Education of Basic Medical Sciences(Southerm Medical University).
文摘Although somatic cells can be reprogrammed to pluripotent stem cells(PsCs)with pure chemicals,authentic pluripotency of chemically induced pluripotent stem celis(CipsCs)has never been achieved through tetraploid complementation assay.Spontaneous reprogramming of spermatogonial stem cells(ssCs)was another non-transgenic way to obtain PsCs,but this process lacks mechanistic explanation.Here,we reconstructed the trajectory of mouse SsC reprogramming and developed a five-chemical combination,boosting the reprogramming effciency by nearly 80-to 100-folds.More importantly,chemical induced germline-derived PsCs(5C-gPSCs),but not gpsCs and chemical induced pluripotent stem cells,had authentic pluripotency,as determined by tetraploid complementation.Mechanistically,ssCs traversed through an inverted pathway of in vivo germ ceil development,exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts.Besides,ssC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5c-gPsCs,which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles.Our work sheds ight on the unique regulatory network underpinning SsC reprogramming,providing insights to understand generic mechanisms for cell-fate decision and epigenetic-relateddisorders in regenerative medicine.
