No abstract

Human facial transplantation, a form of composite tissue allotransplantation, has now become a clinical reality. We carried out the world's second partial facial transplantation in April 2006. We reviewed some issues associated with facial transplantation, especially focusing on the individual who underwent the transplant in our department. We discussed surgical indications, techniques, risks versus benefits, informed consent and psychosocial, societal and financial issues of facial transplantation. In our opinion, with the progresses in composite tissue allotransplantation, partial or full facial transplantation is becoming a timely and effective remedy for the significantly disfigured patients. However, there are a lot of problems unsolved, and as we have performed the transplant on only three individuals, no long-term outcome data are available. Facial transplantation needs further research.

Background Genome-wide mapping of transcription factor (TF) binding sites is essential to identify a TF's direct target genes in kidney development and diseases. However, due to the cellular complexity of the kidney and limited numbers of a given cell type, it has been challenging to determine the binding sites of a TF in vivo. cAMP-response element-binding protein (CREB) is phosphorylated and hyperactive in autosomal dominant polycystic kidney disease (ADPKD). We focus on CREB as an example to profile genomic loci bound by a TF and to identify its target genes using low numbers of specific kidney cells. Methods Cleavage under targets and release using nuclease (CUT&RUN) assays were performed with Dolichos biflorus agglutinin (DBA)-positive tubular epithelial cells from normal and ADPKD mouse kidneys. Pharmacological inhibition of CREB with 666-15 and genetic inhibition with A-CREB were undertaken using ADPKD mouse models. Results CUT&RUN to profile genome-wide distribution of phosphorylated CREB (p-CREB) indicated correlation of p-CREB binding with active histone modifications (H3K4me3 and H3K27ac) in cystic epithelial cells. Integrative analysis with CUT&RUN and RNA-sequencing revealed CREB direct targets, including genes involved in ribosome biogenesis and protein synthesis. Pharmacological and genetic inhibition of CREB suppressed cyst growth in ADPKD mouse models. Conclusions CREB promotes cystogenesis by activating ribosome biogenesis genes. CUT&RUN, coupled with transcriptomic analysis, enables interrogation of TF binding and identification of direct TF targets from a low number of specific kidney cells.