Parthenogenesis is one of the main, and most useful, methods to derive embryonic stem cells （ESCs）, which may be an important source ofhistocompatible cells and tissues for cell therapy. Here we describe the derivat...Parthenogenesis is one of the main, and most useful, methods to derive embryonic stem cells （ESCs）, which may be an important source ofhistocompatible cells and tissues for cell therapy. Here we describe the derivation and characterization of two ESC lines （hPES-1 and hPES-2） from in vitro developed blastocysts following parthenogenetic activation of human oocytes. Typical ESC morphology was seen, and the expression of ESC markers was as expected for alkaline phosphatase, octamer-binding transcription factor 4, stage-specific embryonic antigen 3, stage-specific embryonic antigen 4, TRA- 1-60, and TRA- 1-81, and there was absence of expression of negative markers such as stage-specific embryonic antigen 1. Expression of genes specific for different embryonic germ layers was detected from the embryoid bodies （EBs） of both hESC lines, suggesting their differentiation potential in vitro. However, in vivo, only hPES-1 formed teratoma consisting of all three embryonic germ layers （hPES-2 did not）. Interestingly, after continuous proliferation for more than 100 passages, hPES-1 cells still maintained a normal 46 XX karyotype; hPES-2 displayed abnormalities such as chromosome translocation after long term passages. Short Tandem Repeat （STR） results demonstrated that the hPES lines were genetic matches with the egg donors, and gene imprinting data confirmed the parthenogenetic origin of these ES cells. Genome-wide SNP analysis showed a pattern typical of parthenogenesis. All of these results demonstrated the feasibility to isolate and establish human parthenogenetic ESC lines, which provides an important tool for studying epigenetic effects in ESCs as well as for future therapeutic interventions in a clinical setting.展开更多
In 1903, Farabee analyzed the heredity of the human digital malformation, brachydactyly, the first recorded disorder of the autosomal dominant Mendelian trait. In 1951, Bell classified this type of brachydactyly as ty...In 1903, Farabee analyzed the heredity of the human digital malformation, brachydactyly, the first recorded disorder of the autosomal dominant Mendelian trait. In 1951, Bell classified this type of brachydactyly as type A1 (BDA1). Over 100 cases from different ethnic groups have so far been reported. However, the real breakthrough in identifying the cause of BDA1 has only taken place in the last few years with the progress of the mapping and identification of one of the genes responsible for this disorder, thus providing an answer for a century old riddle. In this article, we attempt to review the current state of knowledge on the genetic features of BDA1 with its century-old history and signalling pathway of IHH, and also discuss genotype-phenotype correlation not only of BDA1, but also of all types of brachydactyly.展开更多
文摘Parthenogenesis is one of the main, and most useful, methods to derive embryonic stem cells （ESCs）, which may be an important source ofhistocompatible cells and tissues for cell therapy. Here we describe the derivation and characterization of two ESC lines （hPES-1 and hPES-2） from in vitro developed blastocysts following parthenogenetic activation of human oocytes. Typical ESC morphology was seen, and the expression of ESC markers was as expected for alkaline phosphatase, octamer-binding transcription factor 4, stage-specific embryonic antigen 3, stage-specific embryonic antigen 4, TRA- 1-60, and TRA- 1-81, and there was absence of expression of negative markers such as stage-specific embryonic antigen 1. Expression of genes specific for different embryonic germ layers was detected from the embryoid bodies （EBs） of both hESC lines, suggesting their differentiation potential in vitro. However, in vivo, only hPES-1 formed teratoma consisting of all three embryonic germ layers （hPES-2 did not）. Interestingly, after continuous proliferation for more than 100 passages, hPES-1 cells still maintained a normal 46 XX karyotype; hPES-2 displayed abnormalities such as chromosome translocation after long term passages. Short Tandem Repeat （STR） results demonstrated that the hPES lines were genetic matches with the egg donors, and gene imprinting data confirmed the parthenogenetic origin of these ES cells. Genome-wide SNP analysis showed a pattern typical of parthenogenesis. All of these results demonstrated the feasibility to isolate and establish human parthenogenetic ESC lines, which provides an important tool for studying epigenetic effects in ESCs as well as for future therapeutic interventions in a clinical setting.
基金This project was supported by NSFC/RGC joint Research Grant(No.N-HKU705/02)the Major State Basic Research Development Program of China(No.2001CB5 10301).
文摘In 1903, Farabee analyzed the heredity of the human digital malformation, brachydactyly, the first recorded disorder of the autosomal dominant Mendelian trait. In 1951, Bell classified this type of brachydactyly as type A1 (BDA1). Over 100 cases from different ethnic groups have so far been reported. However, the real breakthrough in identifying the cause of BDA1 has only taken place in the last few years with the progress of the mapping and identification of one of the genes responsible for this disorder, thus providing an answer for a century old riddle. In this article, we attempt to review the current state of knowledge on the genetic features of BDA1 with its century-old history and signalling pathway of IHH, and also discuss genotype-phenotype correlation not only of BDA1, but also of all types of brachydactyly.
