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Göteborgs universitets publikationer

Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines

Författare och institution:
Nidal Ghosheh (Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin); B. Olsson (-); J. Edsbagge (-); B. Kuppers-Munther (-); M. Van Giezen (-); A. Asplund (-); T. B. Andersson (-); P. Bjorquist (-); Helena Carén (Sahlgrenska Cancer Center & Institutionen för biomedicin, avdelningen för patologi); Stina Simonsson (Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin); P. Sartipy (-); J. Synnergren (-)
Publicerad i:
Stem Cells International, s. Article ID 8648356
ISSN:
1687-966X
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2016
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Medicinska grundvetenskaper ->
Cell- och molekylärbiologi ->
Cellbiologi
Nyckelord:
hepatocyte-like cells, liver development, transcription factors, expansion, endoderm, mesoderm, models, injury, sox17, Cell Biology
Postens nummer:
235935
Posten skapad:
2016-05-04 13:06

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