Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse RLSC and MMH-D3 cell lines

ABSTRACT: Increasing evidence provide support that the mammalian liver contains stem/progenitor cells, but their molecular phenotype, embryological derivation, cell biology as well as of their role in the liver cell turnover and regeneration remain to be further clarified. We report the isolation, characterization and reproducible establishment in line of a resident liver stem cell (RLSC) with immunophenotype and differentiative potential distinct from other previously reported liver precursor/stem cells. RLSCs, derived from foetal and neonatal murine livers as well as from immortalized hepatocytic MMH lines and established in lines, are Sca+, CD34-, CD45-, alfa-fetoprotein+, albumin-. This immunophenotype suggests a non-haematopoietic origin. RLSCs transcriptional profile, defined by microArray technology, highlighted the expression of a broad spectrum of âplasticity-related genesâ and âdevelopmental genesâ suggesting a multi-differentiative potential. RLSCs, indeed, spontaneously differentiate into hepatocytes and cholangiocytes and, when cultured in appropriate conditions, into mesenchymal and neuro-ectodermal cell lineages, such as osteoblasts/osteocytes, chondrocytes, astrocytes and neuronal cells. RLSCs capability to spontaneously differentiate into hepatocytes, the lack of albumin expression and the broad differentiative potentiality locate them in a pre-hepatoblast/liver precursor cells hierarchical position. In conclusion, RLSCs may provide an useful tool to improve liver stem cell knowledge and to assess new therapeutic approaches for liver diseases. Experiment Overall Design: We compared the gene expression profile of a RLSC line to that of the previously characterised hepatocytic differentiated cell line MMH-D3 (ref Amicone), using Affymetrix Mouse430_2 GeneChip array.

ORGANISM(S): Mus musculus

SUBMITTER: Rossella Manfredini

PROVIDER: E-GEOD-7038 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:T-cell acute lymphoblastic leukemia (T-ALL) is mostly characterized by specific chromosomal abnormalities, some occurring in a mutually exclusive manner possibly delineating specific T-ALL subgroups. One subgroup, including MLL-rearranged, CALM-AF10 or inv(7)(p15q34) cases, is characterized by elevated expression of HOXA genes. Using a gene expression based clustering analysis of 67 T-ALL cases with recurrent molecular genetic abnormalities and 25 samples lacking apparent aberrations, we identified 5 new cases with elevated HOXA levels. Using array-CGH, a cryptic and recurrent deletion, del(9)(q34.11q34.13), was exclusively identified in 3 of these 5 cases. This deletion results in a conserved SET-NUP214 fusion product, that was also identified in the T-ALL cell line LOUCY. SET-NUP214 binds in the promoter regions of specific HOXA genes, where it may interact with CRM1 and DOT1L leading to the transcriptional activation of HOXA genes. Targeted inhibition of SET-NUP214 by siRNA abolished expression of HOXA genes, inhibited proliferation and induced differentiation in LOUCY but not in other T-ALL lines. We conclude that SET-NUP214 may contribute to the pathogenesis of T-ALL by enforcing T-cell differentiation arrest. We combined gene expression profiling and array-CGH analysis to detect a new and recurrent molecular cytogenetic abnormality in T-ALL patients that co-clustered with 5 well-defined HOXA-activated T-ALL samples. We describe the cloning of a recurrent SET-NUP214 fusion product in these samples, and identified a potential mechanism by which SET-NUP214 may activate the HOXA gene cluster as potential leukemogenic event in T-ALL. Experiment Overall Design: For 67 T-ALL patients having one of the major molecular cytogenetic abnormalities (i.e. TAL1 (n=24), LMO2 (n=9), HOXA (n=5), HOX11/TLX1 (n=7), and HOX11L2/TLX3 (n=22)), differentially expressed probesets were calculated from Affymetrix U133plus2.0 data based upon a Wilcoxon analysis and corrected for multiple testing for each probeset. Significant and differentially expressed probesets were obtained for the TAL1, HOX11 and HOX11L2 subgroups. No significant probesets were obtained for the HOXA subgroup or the LMO2 subgroup . As TAL1 and LMO2 both participate in the same transcriptional complex, activation of these genes may both lead to a highly similar expression profile. Combined analysis of TAL1 and LMO2 rearranged cases revealed significant and differentially expressed probesets that, as expected, almost entirely overlapped with the gene signature obtained for the TAL1-subgroup only. Next, we clustered 92 T-ALL cases, that besides the 67 cases as described above further included 25 T-ALL that lacked any of these recurrent abnormalities. Cluster analysis was performed based upon the top 25, 50 or 100 most significant probesets for the TAL1, TAL1/LMO2, HOX11 and HOX11L2 subgroups combined with 15 HOXA probesets identified by Soulier et al (2005)

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Transcription profiling of mouse RLSC and MMH-D3 cell lines

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