Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Different propensity in hematopoietic differentiation potential among distinct human pluripotent stem cell lines

ABSTRACT: Lineage-specific differentiation potential varies among different human pluripotent stem cell (hPSC) lines. A stem cell bank may advice researchers on which hPSCs exhibit the highest differentiation potential for a certain lineage. In this study, we aimed at characterizing the hematopoietic differentiation potential from 14 hESC/iPSC lines through the embryoid body (hEB) differentiation system. We carried out gene expression profiling on six different hESC lines grouped according to their ability to differentiate towards hematopoietic lineage: SHEF1, AND1 and H1 were considered as good (high CD45 expression and high CFU potential), whereas H9, HS181 and VAL3 were selected as poor-blood differentiating lines (low CD45 expression and low CFU potential). Human ESC samples were collected during the exponential cell growth phase and stabilized in RNA later. 500 ng of each total RNA sample was labelled with Cy3 using the Quick-Amp Labelling kit and hybridized with the Gene Expression Hybridization kit to a Whole Human Genome Oligo Microarray (Agilent Technologies) following the Manufacturer’s instructions. Each cell line was analyzed as independent duplicates. H9 hESC line was used as the baseline.

ORGANISM(S): Homo sapiens

SUBMITTER: Gustavo Melen

PROVIDER: E-GEOD-23091 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Nodal/Activin signaling predicts human pluripotent stem cell lines prone to differentiate toward the hematopoietic lineage.

Ramos-Mejia Veronica V Melen Gustavo J GJ Sanchez Laura L Gutierrez-Aranda Ivan I Ligero Gertrudis G Cortes Jose L JL Real Pedro J PJ Bueno Clara C Menendez Pablo P

Molecular therapy : the journal of the American Society of Gene Therapy 20100824 12

Lineage-specific differentiation potential varies among different human pluripotent stem cell (hPSC) lines, becoming therefore highly desirable to prospectively know which hPSC lines exhibit the highest differentiation potential for a certain lineage. We have compared the hematopoietic potential of 14 human embryonic stem cell (hESC)/induced pluripotent stem cell (iPSC) lines. The emergence of hemogenic progenitors, primitive and mature blood cells, and colony-forming unit (CFU) potential was an ...[more]

PMID: 20736931

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Project description:The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute lymphoblastic leukemia in infants. Although it is well-established that MLL-AF4 arises pre-natally during human development, its effects on hematopoietic development in utero remains unexplored. We have created a human-specific in vitro system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells (hESCs). Differentiation and functional studies as well as clonal analyses and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. It enhances the specification of hemogenic precursors from hESCs and impairs further hematopoietic commitment of these precursors in favour of the endothelial cell fate. Similar to that reported in cord blood CD34+ hematopoietic stem/progenitor cells (HSPCs), MLL-AF4 expression is not sufficient to transform hESC-derived hematopoietic cells in vitro or in vivo, indicating that additional events may be required to initiate leukemogenesis or that embryonic hematopoiesis is not the appropriate human cellular target for MLL-AF4-mediated leukemogenesis. This work illustrates how hESCs can provide unique insights into human development and further our understanding of how leukemic fusion genes known to arise pre-natally regulate human embryonic hematopoietic specification. MLL is involved in transcriptional regulation and most MLL translocations appear to result in increased expression of Hox genes and hematopoietic genes. We therefore assessed the impact of MLL-AF4 expression on the transcriptome of hESCs. Gene expression profiling performed in MLL-AF4 hESCs revealed that MLL-AF4 preferentially activates transcription. 1826 out of the 3001 genes (61%) expressed were up-regulated in MLL-AF4 hESCs. Human ESC samples were collected during the exponential cell growth phase and stabilized in RNA later. 500 ng of each total RNA sample was labelled with Cy3 using the Quick-Amp Labelling kit and hybridized with the Gene Expression Hybridization kit to a Whole Human Genome Oligo Microarray (Agilent Technologies) following the Manufacturer’s instructions. Each cell line was analyzed as independent duplicates. NEO-expressing (empty lentivector) hESC line was used as the baseline.

Dataset Information

Different propensity in hematopoietic differentiation potential among distinct human pluripotent stem cell lines

Publications

Nodal/Activin signaling predicts human pluripotent stem cell lines prone to differentiate toward the hematopoietic lineage.

Similar Datasets

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