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Reprogramming of Human Fibroblasts into Hematopoietic Progenitors by Fusion With Human Fetal Liver CD34+ Cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE23416 | GEO | 2011/08/04

SECONDARY ACCESSION(S): PRJNA131015

REPOSITORIES: GEO

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Reprogramming of embryonic human fibroblasts into fetal hematopoietic progenitors by fusion with human fetal liver CD34+ cells.

Project description:Experiments with somatic cell nuclear transfer, inter-cellular hybrid formation_ENREF_3, and ectopic expression of transcription factors have clearly demonstrated that cell fate can be dramatically altered by changing the epigenetic state of cell nuclei. Here we demonstrate, using chemical fusion, direct reprogramming of the genome of human embryonic fibroblasts (HEF) into the state of human fetal liver hFL CD34+ (hFL) hematopoietic progenitors capable of proliferating and differentiating into multiple hematopoietic lineages. We show that hybrid cells retain their ploidy and can differentiate into several hematopoietic lineages. Hybrid cells follow transcription program of differentiating hFL cells as shown by genome-wide transcription profiling. Using whole-genome single nucleotide polymorphism (SNP) profiling of both donor genomes we demonstrate reprogramming of HEF genome into the state of hFL hematopoietic progenitors. Our results prove that it is possible to convert the fetal somatic cell genome into the state of fetal hematopoietic progenitors by fusion. This suggests a possibility of direct reprogramming of human somatic cells into tissue specific progenitors/stem cells without going all the way back to the embryonic state. Direct reprogramming of terminally differentiated cells into the tissue specific progenitors will likely prove useful for the development of novel cell therapies.

| S-EPMC3077375 | biostudies-literature

Reprogramming of Human Fibroblasts into Hematopoietic Progenitors by Fusion With Human Fetal Liver CD34+ Cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2011-08-04 | E-GEOD-23416 | biostudies-arrayexpress

Reprogramming of Human Fibroblasts into Hematopoietic Progenitors by Fusion With Human Fetal Liver CD34+ Cells (GenomeWideSNP_6)

Project description:Reprogramming of the human fibroblast genome into the state of the hematopoietic progenitors

2011-08-04 | GSE23414 | GEO

Reprogramming of Human Fibroblasts into Hematopoietic Progenitors by Fusion With Human Fetal Liver CD34+ Cells (GenomeWideSNP_6)

Project description:Reprogramming of the human fibroblast genome into the state of the hematopoietic progenitors Two samples analyzed.

2011-08-03 | E-GEOD-23414 | biostudies-arrayexpress

Reprogramming of Human Fibroblasts into Hematopoietic Progenitors by Fusion With Human Fetal Liver CD34+ Cells (RNA-Seq)

Project description:Reprogramming of the human fibroblast genome into the state of the hematopoietic progenitors

2011-08-04 | GSE23415 | GEO

Reprogramming of Human Fibroblasts into Hematopoietic Progenitors by Fusion With Human Fetal Liver CD34+ Cells (RNA-Seq)

Project description:Reprogramming of the human fibroblast genome into the state of the hematopoietic progenitors One sample analyzed.

2011-08-04 | E-GEOD-23415 | biostudies-arrayexpress

Reprogramming of Human Fibroblasts into Hematopoietic Progenitors by Fusion With Human Fetal Liver CD34+ Cells (HuGene-1_0-st)

Project description:Reprogramming of the human fibroblast genome into the state of the hematopoietic progenitors

2011-08-04 | GSE23413 | GEO

Reprogramming of Human Fibroblasts into Hematopoietic Progenitors by Fusion With Human Fetal Liver CD34+ Cells (HuGene-1_0-st)

Project description:Reprogramming of the human fibroblast genome into the state of the hematopoietic progenitors Five samples analyzed.

2011-08-03 | E-GEOD-23413 | biostudies-arrayexpress

Reprogramming of Human Fibroblasts into Hematopoietic Progenitors by Fusion With Human Fetal Liver CD34+ Cells

Project description:Reprogramming of Human Fibroblasts into Hematopoietic Progenitors by Fusion With Human Fetal Liver CD34+ Cells

| PRJNA131015 | ENA

Senescence induction in human fibroblasts and hematopoietic progenitors by leukemogenic fusion proteins.

Project description:Hematologic malignancies are typically associated with leukemogenic fusion proteins, which are required to maintain the oncogenic state. Previous studies have shown that certain oncogenes that promote solid tumors, such as RAS and BRAF, can induce senescence in primary cells, which is thought to provide a barrier to tumorigenesis. In these cases, the activated oncogene elicits a DNA damage response (DDR), which is essential for the senescence program. Here we show that 3 leukemogenic fusion proteins, BCR-ABL, CBFB-MYH11, and RUNX1-ETO, can induce senescence in primary fibroblasts and hematopoietic progenitors. Unexpectedly, we find that senescence induction by BCR-ABL and CBFB-MYH11 occurs through a DDR-independent pathway, whereas RUNX1-ETO induces senescence in a DDR-dependent manner. All 3 fusion proteins activate the p38 MAPK pathway, which is required for senescence induction. Our results reveal diverse pathways for oncogene-induced senescence and further suggest that leukemias harbor genetic or epigenetic alterations that inactivate senescence induction genes.

| S-EPMC2890151 | biostudies-literature

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