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Glycyrrhizic Acid Inhibits Myeloid Differentiation of Hematopoietic Stem Cells and Improves Cognition in Aged Mice by Binding to the S100 Calcium-Binding Protein A8 [OEA8-67-69 RNA-seq]

ABSTRACT: Glycyrrhizic acid (GA) has numerous biological activities, but the mechanism by which it regulates the immune system and improves cognition in aged mice remains unclear. In this study, we analyzed single-cell sequencing data of peripheral blood mononuclear cells from young mice, aged mice, and GA-treated aged mice, and found that GA reduced senescence-induced increases in macrophages and neutrophils, and increased numbers of lymphoid lineage subpopulations specifically reduced by senescence. In vitro, GA significantly promoted differentiation of Lin-CD117+ hematopoietic stem cells toward lymphoid lineages, especially CD8+ T cells. Moreover, GA inhibited differentiation of CD4+ T cells and myeloid (CD11b+) cells by binding to the S100 calcium-binding protein 8 (S100A8). Overexpression of S100A8 in Lin- CD117+ hematopoietic stem cells enhanced cognition in aged mice and in immune reconstited severely immunodeficient B-NDG mice. Collectively, our results suggest that GA exerts anti-aging effects by binding to S100A8 to remodel the immune system of aged mice. We implemented transcriptomic analyses of HSC (Overexpression of S100A8 and Overexpression of S100A8 with point mutation (aa 67 or aa 69) ).

ORGANISM(S): Mus musculus

PROVIDER: GSE216597 | GEO | 2023/07/14

REPOSITORIES: GEO

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Glycyrrhizic Acid Inhibits Myeloid Differentiation of Hematopoietic Stem Cells and Improves Cognition in Aged Mice by Binding to the S100 Calcium-Binding Protein A8 [scRNA-seq]

Project description:Glycyrrhizic acid (GA) has numerous biological activities, but the mechanism by which it regulates the immune system and improves cognition in aged mice remains unclear. In this study, we analyzed single-cell sequencing data of peripheral blood mononuclear cells from young mice, aged mice, and GA-treated aged mice, and found that GA reduced senescence-induced increases in macrophages and neutrophils, and increased numbers of lymphoid lineage subpopulations specifically reduced by senescence. In vitro, GA significantly promoted differentiation of Lin-CD117+ hematopoietic stem cells toward lymphoid lineages, especially CD8+ T cells. Moreover, GA inhibited differentiation of CD4+ T cells and myeloid (CD11b+) cells by binding to the S100 calcium-binding protein 8 (S100A8). Overexpression of S100A8 in Lin- CD117+ hematopoietic stem cells enhanced cognition in aged mice and in immune reconstited severely immunodeficient B-NDG mice. Collectively, our results suggest that GA exerts anti-aging effects by binding to S100A8 to remodel the immune system of aged mice.

2023-07-14 | GSE216599 | GEO

Glycyrrhizic Acid Inhibits Myeloid Differentiation of Hematopoietic Stem Cells and Improves Cognition in Aged Mice by Binding to the S100 Calcium-Binding Protein A8 [lenti-A8 RNA-seq]

2023-07-14 | GSE216598 | GEO

Glycyrrhizic Acid Inhibits Myeloid Differentiation of Hematopoietic Stem Cells and Improves Cognition in Aged Mice by Binding to the S100 Calcium-Binding Protein A8 [HSC+GA RNA-seq]

2023-07-14 | GSE216596 | GEO

Human Innate Lymphoid Cell Precursors Express CD48 that Modulates ILC Differentiation through 2B4 Signaling

Project description:Innate lymphoid cells (ILCs) develop from common lymphoid progenitors (CLP), which further differentiate into the common ILC progenitor (CILP) that can give rise to both ILCs and NK cells. Murine ILC intermediates have recently been characterized, but the human counterparts and their developmental trajectories have not yet been identified, largely due to the lack of homologous surface receptors in both organisms. Here, we show that human CILPs (CD34+CD117+α4β7+Lin-) acquire CD48 and CD52, which define NK progenitors (NKPs) and innate lymphoid cell precursors (ILCPs). Two distinct NK cell subsets were generated in vitro from CD34+CD117+α4β7+Lin-CD48-CD52+ and CD34+CD117+α4β7+Lin-CD48+CD52+ NKPs, respectively. Independent of NKPs, ILCPs exist in the CD34+CD117+α4β7+Lin-CD48+CD52+ subset and give rise to ILC1s, ILC2s and NCR+ ILC3s, whereas CD34+CD117+α4β7+Lin-CD48+CD52- ILCPs give rise to a distinct subset of ILC3s that have lymphoid tissue inducer (LTi)-like properties. Additionally, CD48 expressing CD34+CD117+α4β7+Lin- precursors give rise to tissue-associated ILCs in vivo. We also observed that the interaction of 2B4 with CD48 induced differentiation of ILC2s, and together these findings show that expression of CD48 by human ILCPs modulates ILC differentiation.

2020-11-20 | GSE160009 | GEO

Gene expression profiling of mouse prostate stem cells

Project description:The mouse prostate tissue exhibits strong power of regeneration, indicating the exisistence of prostate stem cells. Previously we showed that a single mouse prostate cells defined by Lin-CD44+CD133+Sca-1+CD117+ phenotype can generate a prostate after transplantation in vivo. In this study, we compared gene expression profiles of mouse prostate stem cells ( Lin-CD44+CD133+Sca-1+CD117+) and prostate non-stem cells (Lin-CD44-CD133-Sca-1-CD117-). Primary mouse prostate cells were isolated from BL6 mice. Lin-CD44+CD133+Sca-1+CD117+ and Lin-CD44-CD133-Sca-1-CD117- cells were sorted via FACS, and microarray was performed to compare gene expressions between the two groups of cells.

2011-12-06 | E-GEOD-33317 | biostudies-arrayexpress

Long-term Glatiramer Acetate Treatment Induces Subtle Changes in Microglial Transcriptome

Project description:In this study, we investigated the therapeutic potential of a well-tolerated immunomodulatory relapsing-remitting multiple sclerosis drug, glatiramer acetate (GA), on the 3xTg mouse model of Alzheimer's Disease. Briefly, we treated aged female 3xTg mice (>15 mo) weekly with 0.1 mg of GA for 8 weeks. We were able to observe an improvement in cognition and amelioration of amyloid pathology, which we attempted to correlate with changes in microglial transcriptome. To this end, we sorted microglia (CD45int CD11b+) from the hippocampi of GA or PBS-treated 3xTg mice for bulk RNA-seq.

2021-08-27 | GSE169216 | GEO

Gene expression profiling of mouse prostate stem cells

2011-12-06 | GSE33317 | GEO

Fate mapping via Ms4a3 expression history traces monocyte-derived cells

Project description:We performed a single-cell transcriptomic analysis of monocyte and monocyte progenitors by single-cell mRNA sequencing (scRNA-seq) using the C1 Fluidigm platform. We sorted BM cMoPs (Lin−CD117+CD115+CD135−Ly6C+), BM Ly6C+ monocytes (Lin−CD117-CD115+CD135−Ly6C+) and blood Ly6Chi monocytes (CD115+CD11b+Ly6Chi) from wild-type (WT) C57BL/6 mice by fluorescence-activated cell sorting (FACS) and generated transcriptional profiles for each individual cell (n = 38 for blood Ly6Chi monocytes, n = 66 for BM cMoPs, n = 57 for BM Ly6C+ monocytes).

2019-08-19 | GSE134523 | GEO

Systemic human ILC precursors provide a substrate for tissue ILC differentiation

Project description:Innate lymphoid cells (ILC) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. We observed that a population of CD117+ ILC from peripheral blood (PB) of healthy donors does not represent any conical ILC subset, but expressed marker (CD117) commonly expressed by hemato-lymphoid progenitors. We therefore hypothesized PB CD117+ ILC might include uncommitted lymphoid precursors. In order to further understand the identity of PB CD117+ ILC, we profiled the transcriptome of highly purified circulating CD117+ ILC compared to CD34+ HSC, the latter representing immature hematopoietic progenitors with multi-lineage potential. Clear differences in gene expression profiles emerged, with a large cluster of 1540 genes expressed at substantially higher levels in CD117+ ILC. In contrast, CD34+ HSC cells highly expressed genes involved in the broad development of diverse hematopoietic lineages. Compared to HSC, CD117+ ILC express high levels of TF that have been shown to be essential for murine ILC development and we did not detect transcripts characteristic of T and B cells development. Transcriptomic analysis suggested that CD117+ ILC represent lymphoid-biased progenitors carrying a TF expression profile resembling a multi-potent ILC precursor (ILCP).

2017-03-19 | GSE90834 | GEO

Expression data from human mast cell progenitors and mature basophils

Project description:CD34+ CD117+ cells in human peripheral blood have mast cell-forming capacity. We have identified highly committed mast cell progenitors as Lin- CD34+ CD117 intermediate/high FcεRI+ cells. To explore the gene expression profile of the highly committed mast cell progenitors, we performed whole-transcriptome microarray analyses of the cells and compared them with mature basophils.

2015-12-01 | GSE69030 | GEO

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