Author/Authors :
Masahito Tachibana، نويسنده , , Paula Amato، نويسنده , , Michelle Sparman، نويسنده , , Nuria Marti Gutierrez، نويسنده , , Rebecca Tippner-Hedges، نويسنده , , Hong Ma، نويسنده , , Eunju Kang، نويسنده , , Alimujiang Fulati، نويسنده , , Hyo Sang Lee، نويسنده , , Hathaitip Sritanaudomchai، نويسنده , , Keith Masterson، نويسنده , , Janine Larson، نويسنده , , Deborah Eaton، نويسنده , , Karen Sadler-Fredd، نويسنده , , David Battaglia، نويسنده , , David Lee، نويسنده , , Diana Wu، نويسنده , , Jeffrey Jensen Arnett، نويسنده , , Phillip Patton، نويسنده , , Sumita Gokhale، نويسنده , , et al.، نويسنده ,
Abstract :
Reprogramming somatic cells into pluripotent embryonic stem cells (ESCs) by somatic cell nuclear transfer (SCNT) has been envisioned as an approach for generating patient-matched nuclear transfer (NT)-ESCs for studies of disease mechanisms and for developing specific therapies. Past attempts to produce human NT-ESCs have failed secondary to early embryonic arrest of SCNT embryos. Here, we identified premature exit from meiosis in human oocytes and suboptimal activation as key factors that are responsible for these outcomes. Optimized SCNT approaches designed to circumvent these limitations allowed derivation of human NT-ESCs. When applied to premium quality human oocytes, NT-ESC lines were derived from as few as two oocytes. NT-ESCs displayed normal diploid karyotypes and inherited their nuclear genome exclusively from parental somatic cells. Gene expression and differentiation profiles in human NT-ESCs were similar to embryo-derived ESCs, suggesting efficient reprogramming of somatic cells to a pluripotent state.
