Biology subjects

Gao, K.

Publications and source records attributed to Gao, K..

3 recordsLinked to original sources

bioRxiv2018

A potential role for epigenetic processes in the acclimation response to elevated pCO2 in the model diatom Phaeodactylum tricornutum

Understanding of the molecular responses underpinning diatom responses to ocean acidification is fundamental for predicting how important primary producers will be shaped by the continuous rise in atmospheric CO2. In this study, we have analyzed global transcriptomic changes of the model diatom Phaeodactylum tricornutum following growth for 15 generations in elevated pCO2 by strand-specific RNA sequencing (ssRNA-seq). Our results indicate that no significant effects of elevated pCO2 and associated carbonate chemistry changes on the physiological performance of the cells were observed after 15 generations whereas the expression of genes encoding histones and other genes involved in chromatin structure were significantly down-regulated, while the expression of transposable elements (TEs) and genes encoding histone acetylation enzymes were significantly up-regulated. Furthermore, we identified a series of long non-protein coding RNAs (lncRNAs) specifically responsive to elevated pCO2, suggesting putative regulatory roles for these largely uncharacterized genome components. Taken together, our integrative analyses reveal that epigenetic elements such as TEs, histone modifications and lncRNAs may have important roles in the acclimation of diatoms to elevated pCO2 over short time scales and thus may influence longer term adaptive processes in response to progressive ocean acidification.

microbiology↗

bioRxiv2018

Single-cell Transcriptomic Landscape of Nucleated Cells in Umbilical Cord Blood

Umbilical cord blood (UCB) transplant is a therapeutic option for both pediatric and adult patients with a variety of hematologic diseases such as several types of blood cancers, myeloproliferative disorders, genetic diseases, and metabolic disorders. However, the level of cellular heterogeneity and diversity of nucleated cells in the UCB has not yet been assessed in an unbiased and systemic fashion. In the current study, nucleated cells from UCB were subjected to single-cell RNA sequencing, a technology enabled simultaneous profiling of the gene expression signatures of thousands of cells, generating rich resources for further functional studies. Here, we report the transcriptomic maps of 19,052 UCB cells, covering 11 major cell types. Many of these cell types are comprised of distinct subpopulations, including distinct signatures in NK and NKT cell types in the UCB. Pseudotime ordering of nucleated red blood cells (NRBC) identifies wave-like activation and suppression of transcription regulators, leading to a polarized cellular state, which may reflect the NRBC maturation. Progenitor cells in the UBC also consist two subpopulations with divergent transcription programs activated, leading to specific cell-fate commitment. Collectively, we provide this comprehensive single-cell transcriptomic landscape and show that it can uncover previously unrecognized cell types, pathways and gene expression regulations that may contribute to the efficacy and outcome of UCB transplant, broadening the scope of research and clinical innovations.

genomics↗

bioRxiv2017

Inducible and reversible phenotypes in a novel mouse model of Friedreich’s Ataxia

Friedreichs ataxia (FRDA), the most common inherited ataxia, is caused by recessive mutations that reduce the levels of frataxin (FXN), a mitochondrial iron binding protein. We developed an inducible mouse model of Fxn deficiency that enabled us to control the onset and progression of disease phenotypes by the modulation of Fxn levels. Systemic knockdown of Fxn in adult mice led to multiple phenotypes paralleling those observed in human patients across multiple organ systems. By reversing knockdown after clinical features appear, we were able to determine to what extent observed phenotypes represent reversible cellular dysfunction. Remarkably, upon restoration of near wild-type FXN levels, we observed significant recovery of function, associated pathology and transcriptomic dysregulation even after substantial motor dysfunction and pathology were observed. This model will be of broad utility in therapeutic development and in refining our understanding of the relative contribution of reversible cellular dysfunction at different stages in disease.

neuroscience↗