Deletion of B cell master regulators reprogrammed B cells into T cells that were either functional defects or tumorigenic potential. Here we show that Hoxb5, which is expressed in uncommitted hematopoietic progenitors but absent in committed B and T lineages, could reprogram pro-pre-B cells into functional early T cell progenitors. The reprogramming started in bone marrow and completed in thymus, giving rise to T lymphocytes with transcriptomes, hierarchical differentiation, tissue distribution and immune functions closely resembling their natural counterparts. Hoxb5 repressed B cell master genes, activated T cell regulators and regulated crucial chromatin modifiers in pro-pre-B cells, ultimately driving B to T cell fate conversion. Our results provide a de novo paradigm for generating normal and functional T cells through reprogramming in vivo.
Sudden unexplained nocturnal death syndrome (SUNDS) is a perplexing disorder to both forensic pathologists and clinic physicians. Desmoplakin (DSP) gene was the first desmosomal gene linked to arrhythmogenic right ventricular cardiomyopathy (ARVC) which was associated with sudden death. To identify the genetic variants of the DSP gene in SUNDS in the southern Chinese Han population, we genetically screened the DSP gene in 40 sporadic SUNDS victims, 16 Brugada syndrome (BrS) patients and 2 Early Repolarization syndrome (ERS) patients using Next Generation Sequencing (NSG) and direct Sanger sequencing. A total of 10 genetic variants of the DSP gene were detected in 11 cases, comprised of two novel missense mutations (p.I125F and p.D521A) and eight previously reported rare variants. Of eight reported variants, two were previously considered pathogenic (p.Q90R and p.R2639Q), three were predicted in silico to bepathogenic (p.R315C, p.E1357D and p.D2579H), and the rest three were predicted to be benign (p.N1234S, p.R1308Q and p.T2267S). This is the first report of DSP genetic screening in Chinese SUNDS and Brugada syndrome. Our results implies that DSP mutations contribute to the genetic cause of some SUNDS victims and maybe a new susceptible gene for Brugada syndrome.
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