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

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

PROVIDER: PRJNA131015 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR063750.fastq.gz	Fastqsanger.gz

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ATAC-Sequencing of human fetal PreProB and ProB progenitors.

Project description:Human lymphopoiesis is a dynamic life-long process that starts in utero at 6 weeks gestation; however developmental pathways defining fetal lymphopoiesis are largely unexplored. While the first committed B-progenitor in normal human bone marrow (BM) is a CD10+ve ProB-progenitor, the identification of a CD10-ve B-progenitor (Pre/ProB progenitor) in cord blood suggests there may be a second B-lymphoid development program in fetal life. Here, we provide a comprehensive analysis of the fetal B-cell developmental hierarchy and report the presence of both PreProB- and ProB-progenitors in fetal tissues and describe their ontogeny, molecular and functional characteristics. PreProB- and ProB-progenitors appear early in the first trimester in fetal liver, followed by a sustained second wave of B-progenitor development in fetal BM, where together they form >40% of the total HSC/progenitor pool. Unexpectedly, one-third of the B-progenitors (13±1% of lin-CD34+ cells) are CD10-ve PreProB-progenitors while, by contrast, PreProB-progenitors are virtually undetectable in adult BM. Single-cell transcriptomics and functional assays place PreProB- upstream of ProB-progenitors, identifying them as the first B-lymphoid restricted progenitor in human fetal life. Fetal BM PreProB- and ProB-progenitors both give rise solely to B-lineage cells yet they are transcriptionally distinct. PreProB- unlike ProB-progenitors, continue to express a number of key myeloid and stem cell genes and share some transcriptomic signatures with CD10-ve B-progenitor infant acute lymphoblastic leukemia blast cells. Our data identify PreProB-progenitors as the earliest B-lymphoid restricted progenitor in human fetal life, and suggest that this fetal-restricted committed B-progenitor might provide a permissive cellular context for prenatal B-progenitor leukemia initiation.

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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

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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.

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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.

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

2011-08-04 | GSE23413 | GEO

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

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