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Mobilized multipotent hematopoietic progenitors stabilize and expand regulatory T-cells

ABSTRACT: Mobilized multipotent hematopoietic progenitors stabilize and expand regulatory T-cells

PROVIDER: PRJNA648850 | ENA |

REPOSITORIES: ENA

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Mobilized multipotent hematopoietic progenitors stabilize and expand regulatory T-cells

Project description:Objective: Achieving immunoregulation via in vivo expansion of Foxp3+ regulatory CD4+ T cells (Treg) remains challenging. Considerable efforts are being produced aiming at promoting expansion of Tregs in vitro with IL-2, rapamycin, activation with anti-CD3/CD28 mAb-coated beads or with minute foreign antigen doses, for subsequent administration to patients with autoimmune and alloimmune diseases. We have previously shown that mobilized multipotent hematopoietic progenitors (MPPs)collected in peripheral blood stem cell grafts, have the capacity to enhance Treg proliferation in vivo. Design: To analyze the possible mechanisms involved in mouse CD4+CD25high regulatory T-cells (Treg cells) expansion promoted by mobilized MPPs (MPPs), we sequenced and compared the transcriptome of activated Treg extracted from simple culture or from co-culture with MPPs. Results: Tregs cultivated with mobilized MPP had a specialized profile, with enhanced expression of sets of genes coding for receptors and transcription factors that stabilize their regulatory function particularly in inflammatory settings including CD4, CD25 (Il2ra), Foxp3, CD127low (Il7ralpha), Ctla4 high, Tnfrsf18 (Gitr) high, Ikzf2 (Helios) high, Tnfrsf4 (Ox40/CD134) high, Itgae (CD103), regulated by Satb1, Runx, Gata3. Moreover, they exhibit enhanced expression of Prdm1, recently reported to prevent methylation of Foxp3 within Tregs in central nervous system inflammation (14), and Nr4a, that stabilizes Tregs against their differentiation into effector T-cells (15). Their survival is improved by a reduced apoptosis controlled by reduced Tnfrsf1b (p75, Tnfr2) signaling pathway and FOXO-mediated transcription. Their cell cycle is arrested at the G1 stage through enhanced Cdkn1a (p21) and regulated by Runx3 and p53. conclusion: Tregs interacting with mobilized MPP are shaped, stabilized with high immunosuppressive properties.

2020-12-18 | GSE155148 | GEO

Mobilized Multipotent Hematopoietic Progenitors Stabilize and Expand Regulatory T Cells to Protect Against Autoimmune Encephalomyelitis

Project description:Achieving immunoregulation via in vivo expansion of Foxp3+ regulatory CD4+ T cells (Treg) remains challenging. We have shown that mobilization confers to multipotent hematopoietic progenitors (MPPs) the capacity to enhance Treg proliferation. Transcriptomic analysis of Tregs co-cultured with MPPs revealed enhanced expression of genes stabilizing the suppressive function of Tregs as well as the activation of IL-1?–driven pathways. Adoptive transfer of only 25,000 MPPs effectively reduced the development of experimental autoimmune encephalomyelitis (EAE), a pre-clinical model for multiple sclerosis (MS). Production of the pathogenic cytokines IL-17 and GM-CSF by spinal cord-derived CD4+ T-cells in MPP-protected recipients was reduced while Treg expansion was enhanced. Treg depletion once protection by MPPs was established, triggered disease relapse to the same level as in EAE mice without MPP injection. The key role of IL-1? was further confirmed in vivo by the lack of protection against EAE in recipients of IL-1?–deficient MPPs. Mobilized MPPs may thus be worth considering for cell therapy of MS either per se or for enrichment of HSC grafts in autologous bone marrow transplantation already implemented in patients with severe refractory multiple sclerosis.

| S-EPMC7786289 | biostudies-literature

Gene expression analysis of WT and Flt3-ITD multipotent progenitors

Project description:FLT3-ITDs Introduce a Myeloid Differentiation and Transformation Bias in Lympho-myeloid Multipotent Progenitors WT multipotent progenitors were compared with FLT3-ITD multipotent progenitors

2014-05-16 | E-GEOD-35805 | biostudies-arrayexpress

Epigenetic profiling of multipotent progenitors [Bulk_ATACseq_MPP2]

Project description:Epigenetic profiling of multipotent progenitors [Bulk_ATACseq_MPP2]

| PRJNA777786 | ENA

Global Expression profiling of mutant mouse multipotent progenitors.

Project description:Global Expression profiling of mutant mouse multipotent progenitors was performed. In order to mitigate the impact of the studied driver mutations on cell surface phenotypes, we performed transcriptome analysis on a homogeneous population of purified lineage negative, Sca-1/Kit positive multipotent progenitor cells (MPPs, cell surface profile: Lin-/CD34+/Flt3+/CD48+/CD150-). Aprroximately 1000 multipotent progenitors were isolated from wild type or mutant Npm1cA/+, NrasG12D, Npm1cA/+;NrasG12D, Flt3ITD/+ and Npm1cA/+;Flt3ITD/+ murine bone marrow cells. Total RNA extracted and mRNA amplified using

2017-07-30 | E-MTAB-5358 | biostudies-arrayexpress

Apical progenitors remain multipotent throughout cortical neurogenesis

Project description:Apical progenitors remain multipotent throughout cortical neurogenesis

| PRJNA505836 | ENA

Hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs)

Project description:Hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs)

| PRJNA766036 | ENA

Multipotent Progenitors Instruct Ontogeny of the Superior Colliculus

Project description:Multipotent Progenitors Instruct Ontogeny of the Superior Colliculus

| PRJNA1026945 | ENA

Gene expression analysis of WT and Flt3-ITD multipotent progenitors

Project description:FLT3-ITDs Introduce a Myeloid Differentiation and Transformation Bias in Lympho-myeloid Multipotent Progenitors

2014-05-16 | GSE35805 | GEO

miR-125a Confers Multi-Lineage Long-Term Repopulating Stem Cell Activity to Murine and Human Hematopoietic Progenitors

Project description:Umbilical cord blood (CB) is a non-invasive, convenient and broadly used source of hematopoietic stem cells (HSCs) for allogeneic stem cell transplantation. However, limiting numbers of HSCs remain a major constraint for its clinical application. One feasible option would be to expand HSCs to improve therapeutic outcome, however available protocols and the molecular mechanisms governing the self-renewal of HSC are unclear. Here we show that ectopic expression of a single miRNA, miR-125a, in purified murine and human multipotent progenitors (MPP) resulted in increased self-renewal and robust long-term multi-lineage repopulation in transplanted recipient mice. Using quantitative proteomics and Western blot analysis, we identified a restricted set of miR-125a targets which revealed the involvement of the MAP kinase signaling pathway in conferring long-term repopulating capacity to multipotent progenitors in human and mice. Our findings offer the innovative potential to use MPP with enhanced self-renewal activity to augment limited sources of HSC to improve clinical protocols.

2017-01-11 | PXD003931 | Pride

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