In vitro pluripotent stem cell differentiation to hepatocyte ceases further maturation at an equivalent stage of e15 in mouse embryonic liver development

Ravali Raju, David Chau, Tineke Notelaers, Chad L. Myers, Catherine M. Verfaillie, Wei Shou Hu

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Hepatocyte-like cells (HLCs) can be derived from pluripotent stem cells (PSCs) by sequential treatment of chemical cues to mimic the microenvironment of embryonic liver development. However, these HLCs do not reach the full maturity level of primary hepatocytes. In this study, we carried out a meta-Analysis of cross-species transcriptome data of in vitro differentiation of human PSCs to HLCs and in vivo mouse embryonic liver development to identify the developmental stage at which HLC maturation was blocked at. Systematic variations were found associated with the data source and removed by batch correction. Using principal component analysis, HLCs from different stages of differentiation were aligned with mouse embryonic liver development chronologically. A "unified developmental time" (DT) scale was developed after aligning in vitro HLC differentiation and in vivo embryonic liver development. HLCs were found to cease further maturation at an equivalent stage of mouse embryonic day (E)13-15. Genes with discordant time dynamics were identified by aligning in vivo and in vitro data set onto a common DT scale. These genes may be targets of genetic intervention for enhancing the maturity of PSC-derived HLCs.

Original languageEnglish (US)
Pages (from-to)910-921
Number of pages12
JournalStem Cells and Development
Volume27
Issue number13
DOIs
StatePublished - Jul 1 2018

Keywords

  • Gene expression
  • Hepatic differentiation
  • Meta-Analysis
  • Stem cells

Fingerprint Dive into the research topics of 'In vitro pluripotent stem cell differentiation to hepatocyte ceases further maturation at an equivalent stage of e15 in mouse embryonic liver development'. Together they form a unique fingerprint.

Cite this