Biology subjects

Takahashi, S.

Publications and source records attributed to Takahashi, S..

3 recordsLinked to original sources

bioRxiv2017

Genome-wide stability of the DNA replication program in single mammalian cells

Here, we report the establishment of a single-cell DNA replication sequencing method, scRepli-seq, which is a simple genome-wide methodology that measures copy number differences between replicated and unreplicated DNA. Using scRepli-seq, we demonstrate that replication domain organization is conserved among individual mouse embryonic stem cells (mESCs). Differentiated mESCs exhibited distinct replication profiles, which were conserved from cell to cell. Haplotype-resolved scRepli-seq revealed similar replication timing profiles of homologous autosomes, while the inactive X chromosome was clearly replicated later than its active counterpart. However, a small degree of cell-to-cell replication timing heterogeneity was present, and we discovered that developmentally regulated domains are a source of such variability, suggesting a link between cell-to-cell heterogeneity and developmental plasticity. Together, our results form a foundation for single-cell-level understanding of DNA replication regulation and provide insights into 3D genome organization.

genomics↗

bioRxiv2017

ZMYND10 functions in a chaperone relay during axonemal dynein assembly

Molecular chaperones promote the folding and macromolecular assembly of a diverse set of substrate client proteins. How the ubiquitous chaperone machinery directs its activities towards a specific set of substrates and whether this selectivity could be targeted for therapeutic intervention is of intense research. Through the use of mouse genetics, imaging and quantitative proteomics we uncover that ZMYND10 is a novel co-chaperone for the FKBP8-HSP90 chaperone complex during the biosynthesis of axonemal dynein heavy chains required for cilia motility. In the absence of ZMYND10, defects in dynein heavy chains trigger broader dynein motor degradation. We show that FKBP8 inhibition phenocopies dynein motor instability in airway cells, and human disease-causing variants of ZMYND10 disrupt its ability to act as FKBP8-HSP90 co-chaperone. Our study indicates that the motile ciliopathy Primary Ciliary Dyskinesia (PCD) should be considered a cell-type specific protein-misfolding disease and opens the potential for rational drug design that could restore specificity to the ubiquitous chaperone apparatus towards dynein subunits.

cell biology↗

bioRxiv2017

Development of honeybee waggle dance and its differences between recruits and scouts

The lifetime development of the waggle dance of 14 honeybees was automatically recorded just after the imaginal molt using high-definition camera modules connected with a Raspberry Pi computer and numbered radio-frequency identification tags fitted to the back of each bee. For most honeybees, waggle dance follow preceded the appearance of the first waggle dance from 1 week after the imaginal molt. The duration per trip increased just after waggle dance follow. Before the appearance of the first waggle dance, the honeybee repeatedly follows waggle dances that indicate a limited number (2-6) of food source locations. We discriminated between two types of foragers with different roles, recruits and novice scouts, by comparing the vectors indicated by the bees first waggle dance (sending vectors) with dances they had previously followed (received vectors). Of 14 tagged honeybees, 11 were categorized as recruits and 2 as novice scouts. For recruits (but not for novice scouts), the duration per trip increased significantly after waggle dances follow and substantially increased just before the appearance of the first waggle dance. Moreover, recruits increased the number of times they followed waggle dances indicating the same location, and their first waggle dance indicated this location. These results suggest that the differentiation of these two types of foragers is partly related to behavioral differences after waggle dance follows: whether trip is activated or not by follows a waggle dance.\n\nSummary statementBecause of technological difficulties, there are no studies comparing the development of recruit and scout waggle dances. Using miniature radio frequency identification tags, we observed and clarified these developmental processes.\n\nList of Abbreviations

animal behavior and cognition↗