The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis.
AuthorsDi Stefano B, Luo EC, Haggerty C, Aigner S, Charlton J, Brumbaugh J, Ji F, Rabano Jiménez I, Clowers KJ, Huebner AJ, Clement K, Lipchina I, de Kort MAC, Anselmo A, Pulice J, Gerli MFM, Gu H, Gygi SP, Sadreyev RI, Meissner A, Yeo GW, Hochedlinger K
JournalCell Stem Cell
PubMed ID31588046
'Post-transcriptional mechanisms have the potential to influence complex changes in gene expression, yet their role in cell fate transitions remains largely unexplored. Here, we show that suppression of the RNA helicase DDX6 endows human and mouse primed embryonic stem cells (ESCs) with a differentiation-resistant, "hyper-pluripotent" state, which readily reprograms to ... More
Nudt21 Controls Cell Fate by Connecting Alternative Polyadenylation to Chromatin Signaling.
AuthorsBrumbaugh J, Di Stefano B, Wang X, Borkent M, Forouzmand E, Clowers KJ, Ji F, Schwarz BA, Kalocsay M, Elledge SJ, Chen Y, Sadreyev RI, Gygi SP, Hu G, Shi Y, Hochedlinger K
JournalCell
PubMed ID29249356
'Cell fate transitions involve rapid gene expression changes and global chromatin remodeling, yet the underlying regulatory pathways remain incompletely understood. Here, we identified the RNA-processing factor Nudt21 as a novel regulator of cell fate change using transcription-factor-induced reprogramming as a screening assay. Suppression of Nudt21 enhanced the generation of induced ... More
High-throughput, image-based screening of pooled genetic-variant libraries.
AuthorsEmanuel G, Moffitt JR, Zhuang X
JournalNat Methods
PubMed ID29083401
We report a high-throughput screening method that allows diverse genotypes and corresponding phenotypes to be imaged in individual cells. We achieve genotyping by introducing barcoded genetic variants into cells as pooled libraries and reading the barcodes out using massively multiplexed fluorescence in situ hybridization. To demonstrate the power of image-based ... More
Salmonella Persist in Activated Macrophages in T Cell-Sparse Granulomas but Are Contained by Surrounding CXCR3 Ligand-Positioned Th1 Cells.
Salmonella enterica (Se) bacteria cause persistent intracellular infections while stimulating a robust interferon-?-producing CD4
ATP-Dependent Dynamic Protein Aggregation Regulates Bacterial Dormancy Depth Critical for Antibiotic Tolerance.
AuthorsPu Y, Li Y, Jin X, Tian T, Ma Q, Zhao Z, Lin SY, Chen Z, Li B, Yao G, Leake MC, Lo CJ, Bai F
JournalMol Cell
PubMed ID30472191
Cell dormancy is a widespread mechanism used by bacteria to evade environmental threats, including antibiotics. Here we monitored bacterial antibiotic tolerance and regrowth at the single-cell level and found that each individual survival cell shows different "dormancy depth," which in return regulates the lag time for cell resuscitation after removal ... More
The Rational Development of CD133-Targeting Immunotherapies for Glioblastoma.
AuthorsVora P, Venugopal C, Salim SK, Tatari N, Bakhshinyan D, Singh M, Seyfrid M, Upreti D, Rentas S, Wong N, Williams R, Qazi MA, Chokshi C, Ding A, Subapanditha M, Savage N, Mahendram S, Ford E, Adile AA, McKenna D, McFarlane N, Huynh V, Wylie RG, Pan J, Bramson J, Hope K, Moffat J, Singh S
JournalCell Stem Cell
PubMed ID32464096
CD133 marks self-renewing cancer stem cells (CSCs) in a variety of solid tumors, and CD133+ tumor-initiating cells are known markers of chemo- and radio-resistance in multiple aggressive cancers, including glioblastoma (GBM), that may drive intra-tumoral heterogeneity. Here, we report three immunotherapeutic modalities based on a human anti-CD133 antibody fragment that ... More