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Identification of immune-activated Hematopoietic Stem Cells

ABSTRACT: Identification of immune-activated Hematopoietic Stem Cells

PROVIDER: PRJNA418285 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6288320.fastq.gz	Fastqsanger.gz
	SRR6288330.fastq.gz	Fastqsanger.gz
	SRR6288321.fastq.gz	Fastqsanger.gz
	SRR6288331.fastq.gz	Fastqsanger.gz
	SRR6288322.fastq.gz	Fastqsanger.gz

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Operational tolerance after hematopoietic stem cell transplantation is characterized by distinct transcriptional, phenotypic, and metabolic signatures (Cohort 2).

Project description:The mechanisms underlying operational tolerance after hematopoietic stem cell transplantation in humans are poorly understood. We studied two independent cohorts of patients who underwent allogeneic hematopoietic stem cell transplantation from human leukocyte antigen-identical siblings. Primary tolerance was associated with long-lasting reshaping of the recipients' immune system compared to their healthy donors with an increased proportion of regulatory T cell subsets and decreased T cell activation, proliferation, and migration. Transcriptomics profiles also identified a role for nicotinamide adenine dinucleotide biosynthesis in the regulation of immune cell functions. We then compared individuals with operational tolerance and nontolerant recipients at the phenotypic, transcriptomic, and metabolomic level. We observed alterations centered on CD38<sup>+</sup>-activated T and B cells in nontolerant patients. In tolerant patients, cell subsets with regulatory functions were prominent. RNA sequencing analyses highlighted modifications in the tolerant patients' transcriptomic profiles, particularly with overexpression of the ectoenzyme <i>NT5E</i> (encoding CD73), which could counterbalance CD38 enzymatic functions by producing adenosine. Further, metabolomic analyses suggested a central role of androgens in establishing operational tolerance. These data were confirmed using an integrative approach to evaluating the immune landscape associated with operational tolerance. Thus, balance between a CD38-activated immune state and CD73-related production of adenosine may be a key regulator of operational tolerance.

2021-12-22 | MTBLS221 | MetaboLights

Operational tolerance after hematopoietic stem cell transplantation is characterized by distinct transcriptional, phenotypic, and metabolic signatures (Cohort 1).

2021-12-22 | MTBLS220 | MetaboLights

Hematopoietic stem cells (HSCs)

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Identification of immune-activated hematopoietic stem cells.

Project description: Not available

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Immune Reconstitution After Autologous Hematopoietic Stem Cell Transpl for High-Risk Lymphoma

Project description:RATIONALE: Vaccines may help the body build an effective immune response to kill cancer cells. Giving vaccine therapy after an autologous stem cell transplant may kill any cancer cells that remain after transplant. PURPOSE: This clinical trial is studying how well vaccine therapy works in treating patients who have undergone autologous stem cell transplant for high-risk lymphoma or multiple myeloma.

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GNPS - Hematopoietic stem cell derived conditioned media metabolomics

Project description:Metabolomic data of conditioned media derived from culturing hematopoietic stem cells.

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Microarray from both control and activated Hematopoietic stem cells

Project description:Microarray from both control and activated Hematopoietic stem cells

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Identification of immune-activated Hematopoietic Stem Cells

Project description:We utilized our transgenic Fgd5-mCherry mouse to sort and RNAseq for HSCs under acute immune activation (with pIC) to reveal a complex cell cycle gene expression and an upregulated IFN I/II signature

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The CKS1/CKS2 proteostasis axis is crucial to maintain hematopoietic stem cell function

Project description:Long-term hematopoietic stem cells are rare, highly quiescent stem cells of the hematopoietic system with life-long self-renewal potential and the ability to transplant and reconstitute the entire hematopoietic system of conditioned recipients. Most of our understanding of these rare cells has relied on cell surface identification, epigenetic and transcriptomic analyses. Our knowledge of protein synthesis, folding, modification and degradation – broadly termed protein homeostasis or “proteostasis” – in these cells is still in its infancy. Here we report the requirement of the small phospho-binding adaptor proteins, the cyclin dependent kinase subunits (Cks1 and Cks2), for maintaining ordered hematopoiesis and long-term hematopoietic stem cell reconstitution. Cks1 and Cks2 are critical regulators of a myriad of key intracellular signalling pathways that govern hematopoietic stem cell biology and together they balance protein homeostasis and restrain reactive oxygen species to ensure healthy hematopoietic stem cell function.

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Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer

Project description:This clinical trial studies fludarabine phosphate, low-dose total-body irradiation, and donor stem cell transplant followed by cyclosporine, mycophenolate mofetil, and donor lymphocyte infusion in treating patients with hematopoietic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and total body irradiation (TBI) before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also keep the patient’s immune response from rejecting the donor’s stem cells. The donated stem cells may replace the patient’s immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor’s T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body’s normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

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