Abstract
Human embryonic stem cells (hESCs) have the potential to form any cell type in the body, making them attractive cell sources in drug screening, regenerative medicine, disease and developmental processes modeling. However, not all hESC lines have the equal potency to generate desired cell types in vitro. Significant variations have been observed for the differentiation efficiency of various human ESC lines. The precise underpinning molecular mechanisms are still unclear. In this work, we compared transcriptome variations of four hESC lines H7, HUES1, HUES8 and HUES9. We found that hESC lines have different gene expression profiles, and these differentially expressed genes (DEGs) are significantly enriched in developmental processes, such as ectodermal, mesodermal and endodermal development. The enrichment difference between hESC lines was consistent with its lineage bias. Among these DEGs, some pluripotency factors and genes involved in signaling transduction showed great variations as well. The pleiotropic functions of these genes in controlling hESC identity and early lineage specification, implicated that different hESC lines may utilize distinct balance mechanisms to maintain pluripotent state. When the balance is broken in a certain environment, gene expression variation between them could impact on their different lineage specification behavior.
Highlights
Human embryonic stem cells, derived from inner cell mass (ICM) of human blastocysts [1], have the capacity to differentiate into any functional cell type of the three germ layer, and self-renew indefinitely in vitro, making them attractive cell sources in drug screening, regenerative medicine, disease and developmental processes modeling [2,3,4]
Total 19,429 expressed genes were obtained from following RNAseq analysis, including 15,058 protein codings, 1, 841antisenses, 1,058 pseudogenes, 787 long intergenic noncoding RNAs, 287 processed transcripts and 108 micro RNAs (Fig 1B and S1 Table)
Results showed that genes differentially expressed were enriched in developmental process as well (Figure D in S2 Fig). These results suggest that transcriptional variations between Human embryonic stem cells (hESCs) lines are enriched in developmental processes, which could influence their differentiation propensity in vitro
Summary
Human embryonic stem cells (hESCs), derived from inner cell mass (ICM) of human blastocysts [1], have the capacity to differentiate into any functional cell type of the three germ layer (defined as pluripotency), and self-renew indefinitely in vitro, making them attractive cell sources in drug screening, regenerative medicine, disease and developmental processes modeling [2,3,4]. Since the first hESC line established [1], many lines have been cultured from different laboratories in the past two decades around the world [5]. Gene expression variability of hES cell lines no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funder provided support in the form of salaries for CBS, JWZ, DMZ, JW, HMY, XZ, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section
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