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CD38 enzymatic activity promotes hematopoietic stem cell dormancy [bulk RNA-Seq]

ABSTRACT: CD38 enzymatic activity promotes hematopoietic stem cell dormancy [bulk RNA-Seq]

PROVIDER: PRJNA807274 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18034805.fastq.gz	Fastqsanger.gz
	SRR18034806.fastq.gz	Fastqsanger.gz
	SRR18034807.fastq.gz	Fastqsanger.gz
	SRR18034808.fastq.gz	Fastqsanger.gz
	SRR18034809.fastq.gz	Fastqsanger.gz

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CD38 enzymatic activity promotes hematopoietic stem cell dormancy

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CD38 enzymatic activity promotes hematopoietic stem cell dormancy [bulk RNA-Seq]

Project description:Quiescence is a fundamental property that protects hematopoietic stem cells’ (HSCs) function throughout life. A subpopulation of deeply quiescent, so-called dormant HSCs (dHSCs) harbors the highest long-term blood repopulation capacity and resides at the top of the hematopoietic hierarchy. However, the mechanisms of HSC dormancy remain elusive, mainly due to the absence of surface markers for dHSCs’ prompt isolation. We identified CD38 nicotinamide adenine dinucleotide (NAD+) catabolic ecto-enzyme as a novel surface marker for murine dHSCs. The product of CD38 cyclase activity – cyclic adenosine diphosphate ribose (cADPR), regulates the expression of the transcription factor and cell cycle regulator c-Fos via an increase of cytoplasmic Ca2+ concentration. Strikingly, we uncovered that c-Fos drives HSCs quiescence through the induction of the cell cycle inhibitor p57Kip2 expression. Moreover, we found a similar CD38-dependent mechanism of quiescence regulation for human HSCs, which are CD38 negative. Specifically, we found that CD38 ecto-enzymatic activity at the neighboring CD38-positive cells promote human HSCs’ dormancy. Together, our work reveals how extracellular metabolic cues trigger a signaling cascade blocking HSC cell cycle entrance. Pharmacological manipulations of defined pathway will provide new strategies to modulate HSCs activation upon infections, blood loss or transplantation in clinical practice.

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CD38 enzymatic activity promotes hematopoietic stem cell dormancy [scRNA-Seq]

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Project description:CD38 enzymatic activity promotes hematopoietic stem cell dormancy [scRNA-Seq]

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The enzymatic activities of CD38 enhance CLL growth and trafficking: implications for therapeutic targeting

Project description:The ecto-enzyme CD38 is a marker of unfavorable prognosis for chronic lymphocytic leukemia (CLL) patients and an indicator of activation and proliferation of leukemic cells. Here we show that CD38 is enzymatically active in primary CLL cells and that its forced expression increases disease aggressiveness in a xenograft model. The effect is completely lost when using an enzyme deficient version of CD38 with a single amino-acid mutation. Through the enzymatic conversion of NAD, CD38 increases cytoplasmic Ca2+ concentrations, positively influencing proliferation, chemotaxis, adhesion and matrix digestion. Inhibition of the enzymatic activities of CD38 using the flavonoid kuromanin blocks CLL homing. In a short-term xenograft model using primary cells, kuromanin treatment traps CLL cells in the blood, increasing responses to chemotherapy. Microarrays were performed comparing genetic signature derived from Mec-1 cell line variants, generated infecting cells by lentiviruses carrying the genetic material for a wild-type (CD38WT ) or an enzymatically-inactive form of CD38 (CD38M), grown in vitro and in vivo in NSG mice. GFP+ Mec-1 clones (Mec-1/GFP) were generated with the same protocol and used as control.

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Lin-, CD38-, CD34+ Hematopoietic Stem Cells.

Project description:Lin-, CD38-, CD34+ hematopoietic stem cells. Keywords: other

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CD38 enzymatic activity promotes hematopoietic stem cell dormancy

Project description:This SuperSeries is composed of the SubSeries listed below.

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Transcription profiling of human Lin-, CD38-, CD34+ Hematopoietic Stem Cells.

Project description:Lin-, CD38-, CD34+ hematopoietic stem cells. Experiment Overall Design: this experiment include 1 samples and 6 replicates

2008-06-12 | E-GEOD-3788 | biostudies-arrayexpress