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Fetal liver development

ABSTRACT: 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

ORGANISM(S): Mus musculus

PROVIDER: GSE13363 | GEO | 2009/02/23

SECONDARY ACCESSION(S): PRJNA109779

REPOSITORIES: GEO

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Fetal liver development

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 Mouse hepatoblasts were isolated from E12.5 and E17.5 fetal liver using anti-mouse Dlk monoclonal antibody (mAb) according to a previous report and dissolved in Trizol reagent. The cDNA samples synthesized from total RNA were used for a microarray analysis with the mouse GEM2 microarray. One array, no replicates.

2010-05-05 | E-GEOD-13363 | biostudies-arrayexpress

The basic helix-loop-helix transcription factor Mist1 overexpression in mouse fetal hepatoblast culture

Project description:To identify the molecular mechanism of Mist1 during hepatoblasts differentiation, we performed gene expression analysis in Mist1 over-expressed cells. Dlk+ hepatoblasts derived from E13 fetal livers were purified. Purification of Dlk+ cells were performed using anti-Dlk antibody after hematopoietic cells were removed. Cells were infected with mock or Mist1-overexpressing retroviruses and cultured for 3days with oncostatin M.

2015-03-31 | GSE67406 | GEO

The basic helix-loop-helix transcription factor Mist1 overexpression in mouse fetal hepatoblast culture

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Lgr5+ stem and progenitor cells reside at the apex of a heterogeneous embryonic hepatoblast pool

Project description:During mouse embryogenesis, progenitors within the liver known as hepatoblasts give rise to adult hepatocytes and cholangiocytes. Hepatoblasts, which are specified at E8.5-E9.0, have been regarded as a homogeneous progenitor population that initiate differentiation from E13.5. Recently, scRNA-seq analysis has identified sub- populations of transcriptionally distinct hepatoblasts at E11.5. Here, we show that hepatoblasts are not only transcriptionally but also functionally heterogeneous, and that a subpopulation of E9.5-E10.0 hepatoblasts exhibit a previously unidentified early commitment to cholangiocyte fate. Importantly, we also identify a sub-population constituting 2% of E9.5-E10.0 hepatoblasts that express the adult stem cell marker Lgr5, and generate both hepatocyte and cholangiocyte progeny that persist for the lifespan of the mouse. Combining lineage tracing and scRNA-seq, we show that Lgr5 marks E9.5-E10.0 bipotent liver progenitors residing at the apex of a hepatoblast hierarchy. Notably, isolated Lgr5+ hepatoblasts can be clonally expanded in vitro into embryonic liver organoids, which can commit to either hepatocyte or cholangiocyte fates. Our study demonstrates functional heterogeneity within E9.5 hepatoblasts and identifies Lgr5 as a marker for a sub-population of bipotent liver progenitors.

2019-05-27 | GSE123103 | GEO

Expression of genes in adult hepatocytes and fetal hepatoblasts

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

A single-cell transcriptomic analysis reveals precise pathways and regulatory mechanisms underlying hepatoblast differentiation

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.

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Genome-wide analysis of gene expression using in vitro cultured control and Lats1/2 deficient hepatoblasts [RNA-Seq]

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2018-11-07 | GSE85934 | GEO

Characterization of the mid-foregut transcriptome identifies genes regulated during lung bud induction.

Project description:To identify genes expressed during initiation of lung organogenesis, we generated transcriptional profiles of the prospective lung region of the mouse foregut (mid-foregut) microdissected from embryos at three developmental stages between embryonic day 8.5 (E8.5) and E9.5. This period spans from lung specification of foregut cells to the emergence of the primary lung buds. We identified a number of known and novel genes that are temporally regulated as the lung bud forms. Genes that regulate transcription, including DNA binding factors, co-factors, and chromatin remodeling genes, are the main functional groups that change during lung bud formation. Members of key developmental transcription and growth factor families, not previously described to participate in lung organogenesis, are expressed in the mid-foregut during lung bud induction. These studies also show early expression in the mid-foregut of genes that participate in later stages of lung development. This characterization of the mid-foregut transcriptome provides new insights into molecular events leading to lung organogenesis. Three samples (developmental stages), three biological replicates (5-10 pooled mid-foreguts)

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2013-11-08 | E-GEOD-52192 | biostudies-arrayexpress

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