scholarly journals Selection of cell fate in the organ of Corti involves the integration of Hes/Hey signaling at theAtoh1promoter

Development ◽  
2016 ◽  
Vol 143 (5) ◽  
pp. 841-850 ◽  
Author(s):  
Yassan Abdolazimi ◽  
Zlatka Stojanova ◽  
Neil Segil
2021 ◽  
Vol 134 (9) ◽  

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Kira Allmeroth is first author on ‘ N1-acetylspermidine is a determinant of hair follicle stem cell fate’, published in JCS. Kira conducted the research described in this article while a PhD student in Martin Denzel's lab at the Max Planck Insitute for Biology of Ageing, Cologne, Germany. She is now a postdoc in the Denzel lab, investigating stem cells and metabolism.


Author(s):  
Daisylyn Senna Tan ◽  
Yanpu Chen ◽  
Ya Gao ◽  
Anastasia Bednarz ◽  
Yuanjie Wei ◽  
...  

Abstract Transcription factor-driven cell fate engineering in pluripotency induction, transdifferentiation, and forward reprogramming requires efficiency, speed, and maturity for widespread adoption and clinical translation. Here, we used Oct4, Sox2, Klf4, and c-Myc driven pluripotency reprogramming to evaluate methods for enhancing and tailoring cell fate transitions, through directed evolution with iterative screening of pooled mutant libraries and phenotypic selection. We identified an artificially evolved and enhanced POU factor (ePOU) that substantially outperforms wild-type Oct4 in terms of reprogramming speed and efficiency. In contrast to Oct4, not only can ePOU induce pluripotency with Sox2 alone, but it can also do so in the absence of Sox2 in a three-factor ePOU/Klf4/c-Myc cocktail. Biochemical assays combined with genome-wide analyses showed that ePOU possesses a new preference to dimerize on palindromic DNA elements. Yet, the moderate capacity of Oct4 to function as a pioneer factor, its preference to bind octamer DNA and its capability to dimerize with Sox2 and Sox17 proteins remain unchanged in ePOU. Compared with Oct4, ePOU is thermodynamically stabilized and persists longer in reprogramming cells. In consequence, ePOU: 1) differentially activates several genes hitherto not implicated in reprogramming, 2) reveals an unappreciated role of thyrotropin-releasing hormone signaling, and 3) binds a distinct class of retrotransposons. Collectively, these features enable ePOU to accelerate the establishment of the pluripotency network. This demonstrates that the phenotypic selection of novel factor variants from mammalian cells with desired properties is key to advancing cell fate conversions with artificially evolved biomolecules.


PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191160 ◽  
Author(s):  
Arvind Palanisamy ◽  
Ramaswamy Kannappan ◽  
Zhiqiang Xu ◽  
Audrey Martino ◽  
Matthew B. Friese ◽  
...  

2019 ◽  
Author(s):  
Nadia S. Kurd ◽  
Ashley Hoover ◽  
Jaewon Yoon ◽  
Brian M. Weist ◽  
Ellen A. Robey

ABSTRACTThymocytes bearing αβ T cell receptors (TCRαβ) with high affinity for self-peptide-MHC complexes undergo negative selection or are diverted to alternate T cell lineages, a process termed agonist selection. Among thymocytes bearing TCRs restricted to MHC class I, agonist selection can lead to the development of precursors that can home to the gut and give rise to CD8αα-expressing intraepithelial lymphocytes (CD8αα IELs). The factors that influence the choice between negative selection versus CD8αα IEL development remain largely unknown. Using a synchronized thymic tissue slice model that supports both negative selection and CD8αα̣IEL development, we show that the affinity threshold for CD8αα IEL development is higher than for negative selection. We also investigate the impact of peptide presenting cells and cytokines, and the migration patterns associated with these alternative cell fates. Our data highlight the roles of TCR affinity and the thymic microenvironments on T cell fate.


2020 ◽  
Vol 16 (12) ◽  
pp. e1007578
Author(s):  
Vít Nováček ◽  
Gavin McGauran ◽  
David Matallanas ◽  
Adrián Vallejo Blanco ◽  
Piero Conca ◽  
...  

Phosphorylation of specific substrates by protein kinases is a key control mechanism for vital cell-fate decisions and other cellular processes. However, discovering specific kinase-substrate relationships is time-consuming and often rather serendipitous. Computational predictions alleviate these challenges, but the current approaches suffer from limitations like restricted kinome coverage and inaccuracy. They also typically utilise only local features without reflecting broader interaction context. To address these limitations, we have developed an alternative predictive model. It uses statistical relational learning on top of phosphorylation networks interpreted as knowledge graphs, a simple yet robust model for representing networked knowledge. Compared to a representative selection of six existing systems, our model has the highest kinome coverage and produces biologically valid high-confidence predictions not possible with the other tools. Specifically, we have experimentally validated predictions of previously unknown phosphorylations by the LATS1, AKT1, PKA and MST2 kinases in human. Thus, our tool is useful for focusing phosphoproteomic experiments, and facilitates the discovery of new phosphorylation reactions. Our model can be accessed publicly via an easy-to-use web interface (LinkPhinder).


2021 ◽  
Vol 118 (2) ◽  
pp. e2016425118
Author(s):  
Rinako Nakagawa ◽  
Amparo Toboso-Navasa ◽  
Marta Schips ◽  
George Young ◽  
Leena Bhaw-Rosun ◽  
...  

Affinity maturation depends on how efficiently germinal centers (GCs) positively select B cells in the light zone (LZ). Positively selected GC B cells recirculate between LZs and dark zones (DZs) and ultimately differentiate into plasmablasts (PBs) and memory B cells (MBCs). Current understanding of the GC reaction presumes that cMyc-dependent positive selection of LZ B cells is a competitive affinity-dependent process; however, this cannot explain the production of GC-derived lower-affinity MBCs or retention of GC B cells with varied affinities. Here, by combining single-cell/bulk RNA sequencing and flow cytometry, we identified and characterized temporally and functionally distinct positively selected cMyc+ GC B cell subpopulations. cMyc+ LZ B cell subpopulations enriched with either higher- or lower-affinity cells diverged soon after permissive positive selection. The former subpopulation contained PB precursors, whereas the latter comprised less proliferative MBC precursors and future DZ entrants. The overall affinity of future DZ entrants was enhanced in the LZ through preferential proliferation of higher-affinity cells. Concurrently, lower-affinity cells were retained in GCs and protected from apoptosis. These findings redefine positive selection as a dynamic process generating three distinct B cell fates and elucidate how positive selection ensures clonal diversity for broad protection.


2008 ◽  
Vol 28 (26) ◽  
pp. 6633-6641 ◽  
Author(s):  
Z. Chen ◽  
M. Montcouquiol ◽  
R. Calderon ◽  
N. A. Jenkins ◽  
N. G. Copeland ◽  
...  

2017 ◽  
Vol 28 (11) ◽  
pp. 1530-1538 ◽  
Author(s):  
Anthony S. Eritano ◽  
Arturo Altamirano ◽  
Sarah Beyeler ◽  
Norma Gaytan ◽  
Mark Velasquez ◽  
...  

Asymmetric cell division is the primary mechanism to generate cellular diversity, and it relies on the correct partitioning of cell fate determinants. However, the mechanism by which these determinants are delivered and positioned is poorly understood, and the upstream signal to initiate asymmetric cell division is unknown. Here we report that the endoplasmic reticulum (ER) is asymmetrically partitioned during mitosis in epithelial cells just before delamination and selection of a proneural cell fate in the early Drosophila embryo. At the start of gastrulation, the ER divides asymmetrically into a population of asynchronously dividing cells at the anterior end of the embryo. We found that this asymmetric division of the ER depends on the highly conserved ER membrane protein Jagunal (Jagn). RNA inhibition of jagn just before the start of gastrulation disrupts this asymmetric division of the ER. In addition, jagn-deficient embryos display defects in apical-basal spindle orientation in delaminated embryonic neuroblasts. Our results describe a model in which an organelle is partitioned asymmetrically in an otherwise symmetrically dividing cell population just upstream of cell fate determination and updates previous models of spindle-based selection of cell fate during mitosis.


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