Biology subjects

Fann, Y. C.

Publications and source records attributed to Fann, Y. C..

3 recordsLinked to original sources

bioRxiv2024

Resistance to Naive and Formative Pluripotency Conversion in RSeT Human Embryonic Stem Cells

One of the most important properties of human embryonic stem cells (hESCs) is related to their primed and naive pluripotent states. Our previous meta-analysis indicates the existence of heterogeneous pluripotent states derived from diverse naive protocols. In this study, we have characterized a commercial medium (RSeT)-based pluripotent state under various growth conditions. Notably, RSeT hESCs can circumvent hypoxic growth conditions as required by naive hESCs, in which some RSeT cells (e.g., H1 cells) exhibit much lower single cell plating efficiency, having altered or much retarded cell growth under both normoxia and hypoxia. Evidently, hPSCs lack many transcriptomic hallmarks of naive and formative pluripotency (a phase between naive and primed states). Integrative transcriptome analysis suggests our primed and RSeT hESCs are close to the early stage of post-implantation embryos, similar to the previously reported primary hESCs and early hESC cultures. Moreover, RSeT hESCs did not express naive surface markers such as CD75, SUSD2, and CD130 at a significant level. Biochemically, RSeT hESCs exhibit a differential dependency of FGF2 and co-independency of both Janus kinase (JAK) and TGF{beta} signaling in a cell-line-specific manner. Thus, RSeT hESCs represent a previously unrecognized pluripotent state downstream of formative pluripotency. Our data suggest that human naive pluripotent potentials may be restricted in RSeT medium. Hence, this study provides new insights into pluripotent state transitions in vitro.

cell biology↗

bioRxiv2020

Multivariate Meta-Analysis of Differential Principal Components underlying Human Primed and Naive-like Pluripotent States

The ground or naive pluripotent state of human pluripotent stem cells (hPSCs), which was initially established in mouse embryonic stem cells (mESCs), is an emerging and tentative concept. To verify this important concept in hPSCs, we performed a multivariate meta-analysis of major hPSC datasets via the combined analytic powers of percentile normalization, principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), and SC3 consensus clustering. This vigorous bioinformatics approach has significantly improved the predictive values of the current meta-analysis. Accordingly, we were able to reveal various similarities between some naive-like hPSCs (NLPs) and their human and mouse in vitro counterparts. Moreover, we also showed numerous fundamental inconsistencies between diverse naive-like states, which are likely attributed to interlaboratory protocol differences. Collectively, our meta-analysis failed to provide global transcriptomic markers that support a bona fide human naive pluripotent state, rather suggesting the existence of altered pluripotent states under current naive-like growth protocols.

bioinformatics↗

bioRxiv2019

Interlaboratory Data Variability Contributes to the Differential Principal Components of Human Primed and Naïve-like Pluripotent States in Multivariate Meta-Analysis

Currently, genome-wide data analyses have revealed significant differences between various human naive-like pluripotent states derived from different laboratory protocols, confounding the establishment of defining criteria of human naive pluripotency. Thus, it is imperative to understand the concept concerning the ground or naive pluripotent state of pluripotent stem cells, which was initially established in mouse embryonic stem cells (mESCs). Putative human pluripotency has been proposed, largely based on comparing genome-wide transcriptomic signatures of human pluripotent stem cells (hPSCs) with human pre-implantation embryos and mESCs by several research groups. Current bioinformatics approaches, however, have inevitable conceptual biases and technological limitations, including the choices of datasets, analytic methods, and interlaboratory data variability. In this report, we performed a multivariate meta-analysis of major hPSC datasets via the combined analytic powers of percentile normalization, principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), and SC3 consensus clustering. This vigorous bioinformatics approach has significantly improved the predictive values of the current meta-analysis. Accordingly, we were able to reveal various fundamental inconsistencies between naive-like hPSCs and their human and mouse in vitro counterparts, which are likely attributed to interlaboratory protocol differences. Moreover, our meta-analysis failed to provide global transcriptomic markers that support the putative in vitro human naive pluripotent state, rather suggesting the existence of altered pluripotent states under current naive-like hPSC growth protocols.

bioinformatics↗