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Inflammatory exposure drives permanent impairment of hematopoietic stem cell self-renewal activity and accelerated aging.

ABSTRACT: Hematopoietic stem cells (HSCs) mediate regeneration of the hematopoietic system following injury, as exemplified by the transient activation of HSCs out of dormancy upon exposure to infection or inflammation. Such challenges have been documented to impair HSC function. However, whether this functional impairment extends beyond the duration of inflammatory exposure is unknown. To assess the effects of repeated inflammatory challenge, wild-type C57BL/6J mice were subjected to a dose escalation regimen of polyinosinic:polycytidylic acid (pI:pC) treatment mimicking viral infection. Unexpectedly, we observed an irreversible depletion of functional HSCs and hallmarks of accelerated aging in LT-HSCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE200979 | GEO | 2022/07/19

REPOSITORIES: GEO

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Inflammatory exposure drives permanent impairment of hematopoietic stem cell self-renewal activity and accelerated aging

Project description:Hematopoietic stem cells (HSCs) mediate regeneration of the hematopoietic system following injury, as exemplified by the transient activation of HSCs out of dormancy upon exposure to infection or inflammation. Such challenges have been documented to impair HSC function. However, whether this functional impairment extends beyond the duration of inflammatory exposure is unknown. To assess the effects of repeated inflammatory challenge, wild-type C57BL/6J mice were subjected to a dose escalation regimen of polyinosinic:polycytidylic acid (pI:pC) treatment mimicking viral infection. Unexpectedly, we observed an irreversible depletion of functional HSCs and hallmarks of accelerated aging in LT-HSCs. In an effort to conclusively assess whether there was molecular evidence of accelerated aging of LT-HSC after sterile inflammation, we performed whole genome bisulfite sequencing and calculated the biological age by applying a multi-tissue DNA methylome clock. LT-HSCs from mice subject to inflammation demonstrated multiple cellular and molecular features of accelerated aging, including increased biological age.

2022-07-19 | GSE200337 | GEO

Expression data from murine hematopoietic stem cells

Project description:Long-term hematopoietic output is dependent on the hematopoietic stem cell (HSC) homeostasis which is maintained by a complex network of molecules. Among these, microRNAs (miRNAs) play crucial roles, while the underlying molecular basis have not been fully demonstrated. Here, we found that miR-21 is enriched in murine HSCs. Then, we generated a polyinosinic:polycytidylic acid (pIpC)-inducible mouse model (miR-21flox/flox:Mx1-Cre) to obtain a specific deletion of miR-21 in hematopoietic system. It was found that mice with conditional knockout of miR-21 exhibit an obvious perturbation of normal hematopoiesis.Further researches reveal that miR-21 deficiency affect HSC homeostasis and function. We used microarrays to detail the global programme of gene expression, and identified distinct classes of up-regulated and down-regulated genes in murine HSCs after miR-21 conditional knockout.

2021-02-08 | GSE131603 | GEO

Transcriptional Profiling of Human Airway Smooth muscle cells from subjects with and without asthma-effects of mimicking viral challenge

Project description:This experiment was to have a look at the transcriptional profiles from subjects with and without asthma following viral challenge, using Polyinosinic:polycytidylic acid (Poly IC) which is a synthetic analog of double-stranded RNA (dsRNA), a molecular pattern associated with viral infection.

2018-10-29 | E-MTAB-7406 | biostudies-arrayexpress

Expression data from control and LRF (leukemia/lymphoma related factor)-deficient mouse LT-HSCs

Project description:LRF, which is encoded by the ZBTB7A gene and formerly known as POKEMON (POK erythroid myeloid ontogenic factor), was originally identified as a PLZF (promyelocytic leukemia zinc finger) homologue interacting with BCL6 (B-cell lymphoma 6). LRF is a transcription factor that is broadly expressed in hematopoietic lineage cells, but its expression is particularly high in erythroblasts and germinal center (GC) B-cells. The goal of this study is to assess the effect of LRF loss on the LT-HSC transcriptome. Nine days after injection of adult mice with polyinosinic polycytidylic acid (pIpc) to activate Cre, total RNAs were isolated from double-sorted LT-HSCs from LRF Flox/+ Mx1-Cre+ and LRF Flox/Flox Mx1-Cre+ mice and processed for microarray analysis. We performed gene expression microarray analysis of FACS-sorted LT-HSCs (LSK IL7Ra-Flt3-CD150+CD48-) to assess the effect of Lrf loss on the LT-HSC transcriptome. Zbtb7a Flox/+ Mx1-Cre+ mice were used as a control to normalize the potential effects of Cre recombinase. LT-HSCs were FACS-sorted from three Lrf knockout (Zbtb7a Flox/Flox Mx1-Cre+) and two control (Zbtb7a Flox/+ Mx1-Cre+) mice, nine days after the first pIpC injection.

2012-10-26 | E-GEOD-41839 | biostudies-arrayexpress

recombinant human epidermal model LC-MS/MS

Project description:Atopic dermatitis (AD) is a serious inflammatory skin disorder characterized by increased levels of proinflammatory cytokines that contribute to a vicious cycle of inflammation. While the in-flammatory recombinant human epidermal (RHE) models related to AD have been established, there is currently lack of comprehensive understanding. To reveal the alterations and identify potential hub genes in AD-related inflammation, related RHE models induced by inflammatory cocktail (polyinosinic-polycytidylic acid, TNF-α, IL-4 and IL-13) are constructed and analyzed through TMT-proteomic in combination with RNA-seq transcriptomic.

2023-08-07 | PXD043085 | Pride

single cell RNA seq of mouse bone marow-derived hematopoietic stem progenitor cells

Project description:Hematopoietic stem cells (HSCs) have been considered to progressively lose the self-renewal and differentiation potentials towards the commitment to each blood lineage. However, recent studies have suggested megakaryocyte progenitors are generated in a close relation with HSCs. In this study, we identified CD201-CD48- or CD48+ CD150+CD34-Kit+Sca-1+Lin- cells as new early megakaryocyte progenitors (MegP) in adult mouse bone marrow by single-cell (sc) transplantation, sc colony assay, sc RT-PCR, and sc RNA-sequencing. These MegP had little repopulating potential in vivo but formed megakaryocyte colonies in vitro. Transcriptome analysis suggested that these MegP lie downstream of HSCs and upstream of multipotent progenitors in a megakaryocyte differentiation pathway. The polyinosinic-polycytidylic acid (polyIC) injection and long-term reconstitution data suggested that a proportion of MegP expand after inflammation and transplantation. Here we propose a new model of HSC differentiation where HSCs give rise to common myeloid progenitors and MegP with little repopulating activity.

2022-07-29 | GSE135013 | GEO

Expression data from control and LRF (leukemia/lymphoma related factor)-deficient mouse LT-HSCs

2012-10-26 | GSE41839 | GEO

RNASeq of mouse, human, and non-human primate primary dermal fibroblasts to poly(I:C) transfection

Project description:Here, we performed RNA-Seq on mRNA isolated from primary dermal fibroblasts of human, mice and multiple non-human primate species transfected with polyinosinic-polycytidylic acid (polyI:C), a synthetic dsRNA analog that invokes a strong interferon-mediated response, or mock transfected.

2019-10-20 | GSE105160 | GEO

Expression profiling of Abelson interactor-1 (Abi-1) deficient hematopoietic progenitor cells.

Project description:Gene expression profile of LSK-enriched population of hematopoietic progenitor cells from Abi-1 KO mice indicates activation of the NFκB pathway. In this dataset, we include the expression data obtained from Lineage-, Sca-1+, cKit+ (LSK)-enriched population of hematopoietic progenitor cells isolated from the bone marow of Abi-1 KO and WT animals. Abi1(fl/fl);Tg (Mx1- cre(-)) or Abi1(fl/fl);Tg (Mx1-cre(+)) mice were subjected to polyinosinic:polycytidylic acid [poly(I:C)]-induced activation of the Cre recombinase under control of the Mx1 promoter to obtain animals with an Abi1(fl/fl);Tg (Mx1-cre(-)) (Abi-1 WT) or Abi1(-/-);Tg (Mx1-cre(+)) (Abi-1 KO) genotype.

2016-06-14 | GSE83288 | GEO

Transcription profiling of rat pancreatic beta-cells in response to double stranded RNA and IFNgamma exposure

Project description:Viral infections and local production of IFNgamma might contribute to beta-cell dysfunction/death in Type 1 diabetes. Double stranded RNA accumulates in the cytosol of viral-infected cells, and exposure of purified rat beta cells to dsRNA (polyinosinic-polycytidylic acid, PIC) in combination with IFNgamma results in beta-cell dysfunction and apoptosis. To elucidate the molecular mechanisms involved in PIC + IFNgamma-effects, we determined the global profile of genes modified by these agents in primary rat beta cells. FACS-purified rat beta cells were cultured for 6 or 24 h in control condition or with IFNgamma, PIC or a combination of both agents. The gene expression profile was analyzed in duplicate with the Affymetrix RG U34A microarray.

2006-06-20 | E-CBIL-11 | biostudies-arrayexpress

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