Biology subjects

Hsu, F.-M.

Publications and source records attributed to Hsu, F.-M..

4 recordsLinked to original sources

bioRxiv2025

Defining the cell and molecular origins of the primate ovarian reserve

The primate ovarian reserve is established during late fetal development and consists of quiescent primordial follicles in the ovarian cortex, each composed of granulosa cells surrounding an oocyte in dictate. As late stages of fetal development are not routinely accessible for study with human tissue, we exploited the evolutionary proximity of the rhesus macaque to investigate primate follicle formation. Similar to human prenatal ovaries, the rhesus also develops multiple types of pre-granulosa (PG) cells, with the majority of primordial follicles derived from PG2 with small variable contributions from PG1. We observed that activated medullary follicles recruit fetal theca cells to establish a two-cell system for sex-steroid hormone production prior to birth, providing a cell-based explanation for mini puberty.

developmental biology↗

bioRxiv2022

MethylSeqLogo: DNA methylation smart sequence logos

BackgroundSequence logos can effectively visualize position specific base preferences evident in a collection of binding sites of some transcription factor. But those preferences usually fall far short of fully explaining binding specificity. Interestingly, some transcription factors bind sites of potentially methylated DNA. For example, MYC binds CpG sites. This may increase binding specificity as such sites are 1) highly under-represented in the genome, and 2) offer additional, tissue specific information in the form of hypo- or hyper-methylation. Fortunately, bisulfite sequencing data suitable to investigate this possibility is readily available. MethodWe developed MethylSeqLogo, an extension of sequence logos which adds DNA methylation information to sequence logos. MethylSeqLogo includes new elements to indicate DNA methylation and under-represented dimers in each position of a set of aligned binding sites. Our method displays information from both DNA strands, and takes into account the sequence context (CpG or other) and genome region (promoter versus whole genome) appropriate to properly assess the expected background dimer frequency and level of methylation. When designing MethylSeqLogo, we took care to preserve the usual sequence logo meaning of heights; in which the relative height of nucleotides within a column represents their proportion in the binding sites, while the absolute height of each column represents information (relative entropy) and the height of all columns added together represents total information. ResultsWe present several figures illustrating the utility of using MethylSeqLogo to summarize data from CpG binding transcription factors. The logos show that unmethylated CpG binding sites are a feature of transcription factors such as MYC and ZBTB33, while some other CpG binding transcription factors, such as CEBPB, appear methylation neutral. We also compare MethylSeqLogo with two previously reported ways to create methylation aware sequence logos. ConclusionsOur freely available software enables users to explore large-scale bisulfite and ChIP sequencing data sets -- and in the process obtain publication quality figures.

bioinformatics↗

bioRxiv2019

Double triage to identify poorly annotated genes in Maize: The missing link in community curation

The sophistication of gene prediction algorithms and the abundance of RNA-based evidence for the maize genome may suggest that manual curation of gene models is no longer necessary. However, quality metrics generated by the MAKER-P gene annotation pipeline identified 17,225 of 130,330 (13%) protein-coding transcripts in the B73 Reference Genome V4 gene set with models of low concordance to available biological evidence. Working with eight graduate students, we used the Apollo annotation editor to curate 86 transcript models flagged by quality metrics and a complimentary method using the Gramene gene tree visualizer. All of the triaged models had significant errors - including missing or extra exons, non-canonical splice sites, and incorrect UTRs. A correct transcript model existed for about 60% of genes (or transcripts) flagged by quality metrics; we attribute this to the convention of elevating the transcript with the longest coding sequence (CDS) to the canonical, or first, position. The remaining 40% of flagged genes resulted in novel annotations and represent a manual curation space of about 10% of the maize genome (~4,000 protein-coding genes). MAKER-P metrics have a specificity of 100%, and a sensitivity of 85%; the gene tree visualizer has a specificity of 100%. Together with the Apollo graphical editor, our double triage provides an infrastructure to support the community curation of eukaryotic genomes by scientists, students, and potentially even citizen scientists.

bioinformatics↗

bioRxiv2018

General characterization of regeneration in Aeolosoma viride

Regeneration has long attracted scientists for its potential to restore lost, damaged or aged tissues and organs. A wide range of studies have conducted on different model organisms on both cellular and molecular levels. Current evidences suggest that a variety of regenerative strategies are developed and used by different species, and their regenerative strategies are highly correlated to their reproductive methods. Our present work focused on the freshwater annelid Aeolosoma viride, which reproduces by paratonic fission and is capable of complete regeneration. We found out that A. viride can regenerate both anterior and posterior end, even with only 3 segments remained. This process is characterized by epimorphosis that involves large amount of cell proliferation which drives the formation of blastema. Cell proliferation and regeneration successful ratio were significantly decreased when treated with microtubule inhibitor taxol or Avi-tubulin dsRNA, which confirmed that cell proliferation served as a key event during regeneration. Together, our data described the regenerative processes of A. viride, which includes high level of cell proliferation and the formation of blastema. Furthermore, our findings demonstrated A. viride as a potential model for the study of regeneration.

developmental biology↗