Polycomb contraction differentially regulates terminal human hematopoietic differentiation programs.

BACKGROUND: Lifelong production of the many types of mature blood cells from less differentiated progenitors is a hierarchically ordered process that spans multiple cell divisions. The nature and timing of the molecular events required to integrate the environmental signals, transcription factor activity, epigenetic modifications, and changes in gene expression involved are thus complex and still poorly understood. To address this gap, we generated comprehensive reference epigenomes of 8 phenotypically defined subsets of normal human cord blood. RESULTS: We describe a striking contraction of H3K27me3 density in differentiated myelo-erythroid cells that resembles a punctate pattern previously ascribed to pluripotent embryonic stem cells. Phenotypically distinct progenitor cell types display a nearly identical repressive H3K27me3 signature characterized by large organized chromatin K27-modification domains that are retained by mature lymphoid cells but lost in terminally differentiated monocytes and erythroblasts. We demonstrate that inhibition of polycomb group members predicted to control large organized chromatin K27-modification domains influences lymphoid and myeloid fate decisions of primary neonatal hematopoietic progenitors in vitro. We further show that a majority of active enhancers appear in early progenitors, a subset of which are DNA hypermethylated and become hypomethylated and induced during terminal differentiation. CONCLUSION: Primitive human hematopoietic cells display a unique repressive H3K27me3 signature that is retained by mature lymphoid cells but is lost in monocytes and erythroblasts. Intervention data implicate that control of this chromatin state change is a requisite part of the process whereby normal human hematopoietic progenitor cells make lymphoid and myeloid fate decisions.

Endo-Lap OR: an innovative "minimally invasive operating room" design.

BACKGROUND: A newly constructed Endoscopic-Laparoscopic operating room (Endo-Lap OR) started to operate in our department in January 2005. A prospective study was conducted to evaluate its feasibility, efficacy, and safety, as well as the staff's satisfaction. PATIENTS AND METHODS: From January 2005 to September 2005, all patients undergoing operation in this Endo-Lap OR were included in the study. The patient's diagnosis, types of operating procedures, incidents of operating failure (either due to the hardware or the software of Endo-Lap OR) that led to a delay in the patient's transfer or that extended the total operating time were recorded. In addition, questionnaires regarding staff satisfaction with the new operating room were distributed to nurses, anesthetists, and surgeons. RESULTS: A total of 640 cases were included in the study period, 245 cases of open surgery, 282 cases of laparoscopic surgery, 82 cases of endoscopic surgery, 17 cases of video-assisted thoracoscopic surgery, and 14 cases of combined endoscopic-laparoscopic surgery. There were no reported incidents of operating failure related to hardware or software problems. The overall staff satisfaction was excellent. CONCLUSIONS: The integration of endoscopic and laparoscopic surgery into this newly constructed Endo-Lap OR is feasible and safe. The running of the operating room was smooth and it received a high level of acceptance and satisfaction from different staff members.