In vitro differentiation of hepatoblasts into hepatocytes
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PROVIDER: PRJNA734790 | ENA |
REPOSITORIES: ENA
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Project description:We differentiated primary mouse E14.5 Dlk1+ hepatoblasts in vitro into hepatocyte-like cells that recapitulated morphological features of hepatocytes. To assess the level of differentiation, we performed RNA-seq analysis and compared gene expression profiles of hepatobalsts, in vitro differentiated hepatocytes and mature hepatocytes isolated from adult mouse livers as a control.
2021-07-26 | GSE176069 | GEO
Project description:RNA-sequencing results with in vitro cultured control and Lats1/2 deficient hepatoblasts, in vitro differentiated control and Lats1/2 deficient hepatocytes and biliary epithelial cells To investigate changes in gene expression by loss of Lats1 and Lats2 during hepatocyte or biliary epithelial cell differentiation, we performed multiplex RNA-sequecing with in vitro cultured hepatoblasts, in vitro differentiated hepatocytes and biliary epithelial cells
2016-06-29 | E-GEOD-71873 | biostudies-arrayexpress
Project description:Integrative epigenomic and transcriptomic characterization of hepatocyte-like cells differentiated in vitro from human induced pluripotent stem cells in comparison with primary human hepatocytes. This study comprises single cell RNA-seq, bulk mRNA-seq, ATAC-seq and RRBS.
| EGAS00001004201 | EGA
Project description:To analyze stem/progenitor cell function, we purified hepatocytes derived from adult livers and fetal hepatoblasts derived from embryonic day 13 livers. Compared gene expression in E13 hepatoblasts and adult hepatocytes derived from C57BL/6NCr mice
2014-04-11 | E-GEOD-56734 | biostudies-arrayexpress
Project description:Here, we developed a new differentiation protocol by mimicking the two-stage development of hepatoblasts to potentiate their transition to hepatic progenitor cells (hiHPCs), which permits the high-efficiency generation of hiHPCs from chemically induced pluripotent stem cells (hCiPSCs). Moreover, hCiPSC-derived hiHPCs can further differentiate into mature hepatocytes (hiHEPs). We use single-cell RNA sequencing (scRNA-seq) to analyze the two-stage of hepatoblasts indicating the similarity between hepatoblasts differentiated in vitro and in vivo. In addition, we show that the global gene expression profile of hiHPCs was indistinguishable from that of human fetal liver cells (hFLCs) and hCiPSC-derived hiHEPs resembled F-PHHs by using RNA sequencing (RNA-seq).
2023-10-10 | GSE233413 | GEO
Project description:RNA-sequencing results with in vitro cultured control and Lats1/2 deficient hepatoblasts, in vitro differentiated control and Lats1/2 deficient hepatocytes and biliary epithelial cells
2016-06-29 | GSE71873 | GEO
Project description:Background & Aims Hepatocytes differentiated from human embryonic stem cells (hESCs) have the potential to overcome the shortage of primary hepatocytes for clinical use and drug development. Many strategies for this process have been reported, but the functionality of the resulting cells is incomplete. We hypothesize that the functionality of hPSC-derived hepatocytes might be improved by making the differentiation method more similar to normal in vivo hepatic development. Methods We tested combinations of growth factors and small molecules targeting candidate signaling pathways culled from the literature to identify optimal conditions for differentiation of hESCs to hepatocytes, using qRT-PCR for stage-specific markers to identify the best conditions. Immunocytochemistry was then used to validate the selected conditions. Finally, induction of expression of metabolic enzymes in terminally differentiated cells was used to assess the functionality of the hESC-derived hepatocytes. Results Optimal differentiation of hESCs was attained using a 5-stage protocol. After initial induction of definitive endoderm (stage 1), we showed that inhibition of the WNT/β-catenin pathway during the 2nd and 3rd stages of differentiation was required to specify first posterior foregut, and then hepatic gut cells. In contrast, during the 4th stage of differentiation, we found that activation of the WNT/β-catenin pathway allowed generation of proliferative bipotent hepatoblasts, which then were efficiently differentiated into hepatocytes in the 5th stage by dual inhibition of TGF-β and NOTCH signaling. Conclusion Here, we show that stage-specific regulation of the WNT/β-catenin pathway results in improved differentiation of hESCs to functional hepatocytes.
2019-03-12 | GSE128102 | GEO
Project description:To analyze stem/progenitor cell function, we purified hepatocytes derived from adult livers and fetal hepatoblasts derived from embryonic day 13 livers.
2014-04-11 | GSE56734 | GEO
Project description:How the bi-potential hepatoblasts differentiate into hepatocytes and cholangiocytes remains unclear. Here, using single-cell transcriptomic analysis of hepatoblasts, hepatocytes, and cholangiocytes sorted from E10.5 to E17.5 mouse embryos, we found that hepatoblast-to-hepatocyte differentiation occurred gradually followed a linear default pathway. As more cells became fully differentiated hepatocytes, the number of proliferating cells decreased. Surprisingly, the proliferating and quiescent hepatoblasts exhibited homogeneous differentiation states at a given developmental stage. This unique feature enabled us to combine the single-cell and bulk-cell analyses to define the precise timing of the hepatoblast-to-hepatocyte transition, which occurs between E13.5 and E15.5. In contrast to hepatocyte development at almost all levels, hepatoblast-to-cholangiocyte differentiation underwent a sharp detour from the default pathway. New cholangiocyte generation occurred continuously between E11.5 and E14.5, but their maturation states at a given developmental stage were heterogeneous. Even more surprising, the number of proliferating cells increased as more progenitor cells differentiated into mature cholangiocytes. Based on an observation from the single-cell analysis, we also discovered that the protein kinase C (PKC)/mitogen-activated protein kinase (MAPK) signaling pathway promoted cholangiocyte maturation. CONCLUSIONS: Our studies have defined distinct pathways for hepatocyte and cholangiocyte development in vivo, which are critically important for understanding basic liver biology and developing effective strategies to induce stem cells to differentiate towards specific hepatic cell fates in vitro.
2017-07-14 | GSE90047 | GEO
Project description:Hepatoblasts emerging at E8.5 from the foregut endoderm proliferate vigorously and differentiate to hepatocytes and biliary epithelial cells. To find genes important for hepatocyte differentiation during development, we compared gene expression profiles of hepatoblasts/immature hepatocytes at E12.5 and E17.5. As Dlk, also known as Pref-1, is expressed in hepatoblasts/immature hepatocytes, we performed a microarray analysis of the Dlk+ cells isolated from livers at E12.5 and E17.5. Keywords: fetal liver cells comparing
2009-02-23 | GSE13363 | GEO