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Gene expression from lamina propria of olfactory mucosa from Human

ABSTRACT: The establishment of induced pluripotent stem (iPS) cells methodologies has widened the possibilities of stem cell related clinical therapies. However, safety concerns over current reprogramming technologies as well as lack of efficient protocols for differentiation raise serious questions over their usage in clinical settings. Direct lineage conversion may represent a safer technology for cell-therapy. Here, we identify Sox2 as a factor able to transdetermine human mesenchymal stem cells (MSCs) to hematopoietic progenitor cells (HPCs), recapitulating the molecular events during in vivo hematopoiesis. This technology offers an efficiency of up to 70% HPC generation in less than 8 days under feeder-free conditions. With the goal of devising ways for transplantation into diseased patients we developed two different methodologies that avoid exogenous DNA integration or viral infections. The first, by transduction of recombinant Sox2 protein, and the second by functional replacement of Sox2 by inhibition of TGFß signaling. The DNA integration-, virus-, and feeder-free transdetermination system here described may complement and enhance current approaches for autologous as well as heterologous HPC transplantation in humans. Mesenchymal Stem Cells were transdifferentiated towards the hematopoietic lineage.

ORGANISM(S): Homo sapiens

SUBMITTER: Ignacio Sancho-Martinez

PROVIDER: E-GEOD-25336 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene expression from lamina propria of olfactory mucosa from Human

Project description:The establishment of induced pluripotent stem (iPS) cells methodologies has widened the possibilities of stem cell related clinical therapies. However, safety concerns over current reprogramming technologies as well as lack of efficient protocols for differentiation raise serious questions over their usage in clinical settings. Direct lineage conversion may represent a safer technology for cell-therapy. Here, we identify Sox2 as a factor able to transdetermine human mesenchymal stem cells (MSCs) to hematopoietic progenitor cells (HPCs), recapitulating the molecular events during in vivo hematopoiesis. This technology offers an efficiency of up to 70% HPC generation in less than 8 days under feeder-free conditions. With the goal of devising ways for transplantation into diseased patients we developed two different methodologies that avoid exogenous DNA integration or viral infections. The first, by transduction of recombinant Sox2 protein, and the second by functional replacement of Sox2 by inhibition of TGFß signaling. The DNA integration-, virus-, and feeder-free transdetermination system here described may complement and enhance current approaches for autologous as well as heterologous HPC transplantation in humans.

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CXCL12/CXCR4 signaling enhances human PSC-derived hematopoietic progenitor function and overcomes early in vivo transplantation failure

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Targeted CpG island methylation in human pluripotent stem cells

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Human iPSCs derived under feeder free conditions displays an unqiue cell cycle and DNA replication genotype

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Paracrine TGFß Signaling Counterbalances BMP-Mediated Repression in Hair Follicle Stem Cell Activation

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Transcription profiling of human gene expression profiles of CD34+/CD38- cells vs AFT024

Project description:It is widely accepted that hematopoietic progenitor cells (HPC) are tightly associated with discrete niches within the bone marrow. This molecular environment supports and regulates their self renewal and differentiation. AFT024 is a cell line derived from murine fetal liver that has been demonstrated to maintain human hematopoietic progenitors in an undifferentiated state in vitro. While various functional and genomic studies of this and other stromal layers have already been reported, the influence of the cellular microenvironment on the gene expression of HPC has not yet been systematically analyzed.<br> <br> The CD34+/CD38- fraction of human umbilical cord blood was parted and either cultivated on AFT024 [kindly provided by I. Lemischka] or without stromal feeder layer for 16h, 20h, 48h or 72h. Both fractions were then harvested and separated by vigorous pipetting and FACS sorted again to separate the HPC from AFT024. Global gene expression profiles were determined using a novel Human Genome cDNA Microarray of over 51,145 ESTs of the UnigenSet-RZPD3. In analogy, we have compared the gene expression profiles of CD34+/CD38- cells versus AFT024 to exclude that differential gene expression resulted from contaminating feeder layer cells.

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Human iPSCs derived under feeder free conditions displays an unqiue cell cycle and DNA replication genotype

2011-06-03 | E-GEOD-21655 | biostudies-arrayexpress