To solve the problem of immune incompatibility, nuclear transplantation has been envisaged as a means to produce cells or tissues for human autologous transplantation. Here we have derived embryonic stem cells by the ...To solve the problem of immune incompatibility, nuclear transplantation has been envisaged as a means to produce cells or tissues for human autologous transplantation. Here we have derived embryonic stem cells by the transfer of human somatic nuclei into rabbit oocytes. The number of blastocysts that developed from the fused nuclear transfer was comparable among nuclear donors at ages of 5, 42, 52 and 60 years, and nuclear transfer (NT) embryonic stem cells (ntES cells) were subsequently derived from each of the four age groups. These results suggest that human somatic nuclei can form ntES cells independent of the age of the donor. The derived ntES cells are human based on karyotype, isogenicity, in situ hybridization, PCR and immunocytochemistry with probes that distinguish between the various species. The ntES cells maintain the capability of sustained growth in an undifferentiated state, and form embryoid bodies, which, on further induction, give rise to cell types such as neuron and muscle, as well as mixed cell populations that express markers representative of all three germ layers. Thus, ntES cells derived from human somatic cells by NT to rabbit eggs retain phenotypes similar to those of conventional human ES cells, including the ability to undergo multilineage cellular differentiation.展开更多
Dear Editor, Human embryonic stem （ES） cells possess the potential to differentiate into all the cell types of the human body and provide potential applications in regenerative medicine . However, the concerns of i...Dear Editor, Human embryonic stem （ES） cells possess the potential to differentiate into all the cell types of the human body and provide potential applications in regenerative medicine . However, the concerns of immune rejection hamper transplantation therapies using human ES cells. To avoid the complications of immune rejection, diverse methods, such as somatic nuclear transfer （also called therapeutic cloning） and fusion of somatic ceils with human ES ceils , have been attempted to produce patient-specific pluripotent stem cells. Most of these approaches have resulted in little success. The generation of human iPS cells （induced展开更多
Transforming growth factor （TGF）-βs and their family members, including bone morphogenetic proteins （BMPs）, Nodal and activins, have been implicated in the development and maintenance of various organs, in which ...Transforming growth factor （TGF）-βs and their family members, including bone morphogenetic proteins （BMPs）, Nodal and activins, have been implicated in the development and maintenance of various organs, in which stem cells play important roles. Stem cells are characterized by their ability to self-renew and to generate differentiated cells of a particular tissue, and are classified into embryonic and somatic stem cells. Embryonic stem （ES） cells self-renew indefinitely and contribute to derivatives of all three primary germ layers. In contrast, somatic stem cells, which can be identified in various adult organs, exhibit limited abilities for self-renewal and differentiation in most cases. The multi-lineage differentiation capacity of ES ceils and somatic stem cells has opened possibilities for cell replacement therapies for genetic, malignant and degenerative diseases. In order to utilize stem cells for therapeutic applications, it is essential to understand the extrinsic and intrinsic factors regulating self-renewal and differentiation of stem cells. More recently, induced pluripotent stem （iPS） cells have been generated from mouse and human fibroblasts that resemble ES cells via ectopic expression of four transcription factors, iPS cells may have an advantage in regenerative medicine, since they overcome the immunogenicity and ethical controversy of ES cells. Moreover, recent studies have highlighted the involvement of cancer stem cells during the formation and progression of various types of cancers, including leukemia, glioma, and breast cancer. Here, we illustrate the roles of TGF-β family members in the maintenance and differentiation of ES cells, somatic stem cells, and cancer stem cells.展开更多
Nanog is a newly identified homeodomain gene that functions to sustain the pluripotency of embryonic stem cells.However,the molecular mechanism through which nanog regulates stem cell pluripotency remains unknown.Mous...Nanog is a newly identified homeodomain gene that functions to sustain the pluripotency of embryonic stem cells.However,the molecular mechanism through which nanog regulates stem cell pluripotency remains unknown.Mouse nanog encodes a polypeptide of 305 residues with a divergent homeodomain similar to those in the NK-2 family.The rest ofnanog contains no apparent homology to any known proteins characterized so far.It is hypothesized that nanog encodes a transcription factor that regulates stem cell pluripotency by switching on or off target genes.To test this hypothesis,we constructed fusion proteins between nanog and DNA binding domains of the yeast transcription factor Gal4 and tested the transactivation potentials of these constructs.Our data demonstrate that both regions N- and C- terminal to the homeodomain have transcription activities.Despite the fact that it contains no apparent transactivation motifs,the C-terminal domain is about 7 times as active as the N-terminal one.This unique arrangement of dual transactivators may confer nanog the flexibility and specificity to regulate downstream genes critical for both pluripotency and differentiation of stem cells.展开更多
基金supported by grants from the Major State Basic Research Development Program of China(No.001CB5099)the National High Technology Research and Development Program of China(No.2001AA216121)+3 种基金National Natural Science Foundation of China(No.30040003)Projects of Shanghai Science&Technology Development Foundation(No.99DJ14002,00DJ14033,01DJ14003)the Chinese Academy of Sciences(No.KSCX-2-3-08)Shanghai Municipal Education Commission and by Shanghai Second Medical University
文摘To solve the problem of immune incompatibility, nuclear transplantation has been envisaged as a means to produce cells or tissues for human autologous transplantation. Here we have derived embryonic stem cells by the transfer of human somatic nuclei into rabbit oocytes. The number of blastocysts that developed from the fused nuclear transfer was comparable among nuclear donors at ages of 5, 42, 52 and 60 years, and nuclear transfer (NT) embryonic stem cells (ntES cells) were subsequently derived from each of the four age groups. These results suggest that human somatic nuclei can form ntES cells independent of the age of the donor. The derived ntES cells are human based on karyotype, isogenicity, in situ hybridization, PCR and immunocytochemistry with probes that distinguish between the various species. The ntES cells maintain the capability of sustained growth in an undifferentiated state, and form embryoid bodies, which, on further induction, give rise to cell types such as neuron and muscle, as well as mixed cell populations that express markers representative of all three germ layers. Thus, ntES cells derived from human somatic cells by NT to rabbit eggs retain phenotypes similar to those of conventional human ES cells, including the ability to undergo multilineage cellular differentiation.
基金Acknowledgment This research was supported by grants from the Ministry of Science and Technology of China （2006CB943901, 2007CB948003） the National Natural Science Foundation of China （30600306, 30623003） Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences （2007KIP 101,2007KIP401）, Chinese Academy of Sciences.
文摘Dear Editor, Human embryonic stem （ES） cells possess the potential to differentiate into all the cell types of the human body and provide potential applications in regenerative medicine . However, the concerns of immune rejection hamper transplantation therapies using human ES cells. To avoid the complications of immune rejection, diverse methods, such as somatic nuclear transfer （also called therapeutic cloning） and fusion of somatic ceils with human ES ceils , have been attempted to produce patient-specific pluripotent stem cells. Most of these approaches have resulted in little success. The generation of human iPS cells （induced
文摘Transforming growth factor （TGF）-βs and their family members, including bone morphogenetic proteins （BMPs）, Nodal and activins, have been implicated in the development and maintenance of various organs, in which stem cells play important roles. Stem cells are characterized by their ability to self-renew and to generate differentiated cells of a particular tissue, and are classified into embryonic and somatic stem cells. Embryonic stem （ES） cells self-renew indefinitely and contribute to derivatives of all three primary germ layers. In contrast, somatic stem cells, which can be identified in various adult organs, exhibit limited abilities for self-renewal and differentiation in most cases. The multi-lineage differentiation capacity of ES ceils and somatic stem cells has opened possibilities for cell replacement therapies for genetic, malignant and degenerative diseases. In order to utilize stem cells for therapeutic applications, it is essential to understand the extrinsic and intrinsic factors regulating self-renewal and differentiation of stem cells. More recently, induced pluripotent stem （iPS） cells have been generated from mouse and human fibroblasts that resemble ES cells via ectopic expression of four transcription factors, iPS cells may have an advantage in regenerative medicine, since they overcome the immunogenicity and ethical controversy of ES cells. Moreover, recent studies have highlighted the involvement of cancer stem cells during the formation and progression of various types of cancers, including leukemia, glioma, and breast cancer. Here, we illustrate the roles of TGF-β family members in the maintenance and differentiation of ES cells, somatic stem cells, and cancer stem cells.
基金supported in part by the Tsinghua University BaiRen Scholar Program,NSFC 30270287the 973 Project--2001CB5101 from The Ministry of Science and Technology of China.
文摘Nanog is a newly identified homeodomain gene that functions to sustain the pluripotency of embryonic stem cells.However,the molecular mechanism through which nanog regulates stem cell pluripotency remains unknown.Mouse nanog encodes a polypeptide of 305 residues with a divergent homeodomain similar to those in the NK-2 family.The rest ofnanog contains no apparent homology to any known proteins characterized so far.It is hypothesized that nanog encodes a transcription factor that regulates stem cell pluripotency by switching on or off target genes.To test this hypothesis,we constructed fusion proteins between nanog and DNA binding domains of the yeast transcription factor Gal4 and tested the transactivation potentials of these constructs.Our data demonstrate that both regions N- and C- terminal to the homeodomain have transcription activities.Despite the fact that it contains no apparent transactivation motifs,the C-terminal domain is about 7 times as active as the N-terminal one.This unique arrangement of dual transactivators may confer nanog the flexibility and specificity to regulate downstream genes critical for both pluripotency and differentiation of stem cells.
