Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE252914 | GEO | 2024/06/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling [mim-tRNAseq]

Project description:High-resolution quantitative profiling of tRNA abundance and modification status in hematopoietic cells upon Trmt6 deletion by mim-tRNAseq

2024-06-03 | GSE252912 | GEO

tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling [scRNA-seq]

Project description:Hematopoietic stem cells (HSCs) have some unique physiological adaptations to maintain blood cell production and deal with stress responses throughout life. To maintain such adaptations, HSCs are particularly dependent on maintaining a tightly controlled protein translation rate. However, how HSCs fine tune protein translation has not been fully described. In this study, we report the role of TRMT6 in regulating HSC function in adult hematopoiesis. Trmt6-null mice became moribund due to hematopoietic failure with pancytopenia in the blood and bone marrow 4 to 8 weeks after Trmt6 deletion. Trmt6-deleted bone marrow cells failed to repopulate hemoablated recipients in competitive transplantation experiments. Loss of TRMT6 resulted in an abnormally high rate of recruitment of quiescent hematopoietic stem cells (HSCs) into the cell cycle. Cycling HSCs produced progenitors at the expense of self-renewal, which led to the exhaustion of the HSC pool. Mechanistically, mTORC1 signaling pathway was highly upregulated in HSC-enriched cell populations after Trmt6 deletion by single cell RNA-seq analysis. Furthermore, TRMT6 was required for tRNA m1A modification required for HSC quiescence and self-renewal. Our data indicate that TRMT6 promotes the expression of TSC1, fine-tuning mTORC1 signaling level which is essential for HSC maintenance and self-renewal in adult hematopoiesis.

2024-06-03 | GSE230711 | GEO

tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling

Project description:tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling

| PRJNA1063223 | ENA

tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling [mim-tRNAseq]

Project description:tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling [mim-tRNAseq]

| PRJNA1063221 | ENA

tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling [scRNA-seq]

Project description:tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling [scRNA-seq]

| PRJNA962329 | ENA

tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis

Project description:Using genetic mouse models, high-throughput sequencing, transcriptome-wide m1A profiling and ribosome profiling, we find: (1) Translation is the most active process of these genetic information processing in early T cell activation. (2) T cells upregulate tRNA-m1A58 “writer” proteins TRMT61A and TRMT6 to install m1A58 modification to a specific subset of early expressed tRNAs during the early stage of activation. (3) m1A58 modifications in tRNA support rapid and adequate synthesis of MYC and other key functional proteins, guide the exit of naïve T cells from quiescence state into a proliferative state, and promote rapid T cell expansion after activation.

2022-07-23 | GSE184909 | GEO

SZT2 maintains hematopoietic stem cell homeostasis via nutrient-mediated mTORC1 regulation.

Project description:The mTORC1 pathway coordinates nutrient and growth factor signals to maintain organismal homeostasis. Whether nutrient signaling to mTORC1 regulates stem cell function remains unknown. Here, we show that SZT2 - a protein required for mTORC1 downregulation upon nutrient deprivation - is critical for hematopoietic stem cell (HSC) homeostasis. Ablation of SZT2 in HSCs decreased the reserve and impaired the repopulating capacity of HSCs. Furthermore, ablation of both SZT2 and TSC1 - 2 repressors of mTORC1 on the nutrient and growth factor arms, respectively - led to rapid HSC depletion, pancytopenia, and premature death of the mice. Mechanistically, loss of either SZT2 or TSC1 in HSCs led to only mild elevation of mTORC1 activity and reactive oxygen species (ROS) production. Loss of both SZT2 and TSC1, on the other hand, simultaneously produced a dramatic synergistic effect, with an approximately 10-fold increase of mTORC1 activity and approximately 100-fold increase of ROS production, which rapidly depleted HSCs. These data demonstrate a critical role of nutrient mTORC1 signaling in HSC homeostasis and uncover a strong synergistic effect between nutrient- and growth factor-mediated mTORC1 regulation in stem cells.

| S-EPMC9566891 | biostudies-literature

Hematopoietic stem cells do not depend on N-cadherin to regulate their maintenance.

Project description:According to the "osteoblastic niche" model, hematopoietic stem cells (HSCs) are maintained by N-cadherin-mediated homophilic adhesion to osteoblasts at the bone marrow endosteum. In contrast to this model, we cannot detect N-cadherin expression by HSCs, and most HSCs do not localize to the endosteal surface. It has nonetheless been suggested that HSCs express low levels of N-cadherin that regulate HSC maintenance. To test this, we conditionally deleted N-cadherin from HSCs and other hematopoietic cells in adult Mx-1-Cre(+)N-cadherin(fl/-) mice. N-cadherin deficiency had no detectable effect on HSC maintenance or hematopoiesis. N-cadherin deficiency did not affect bone marrow cellularity or lineage composition, the numbers of colony-forming progenitors, the frequency of HSCs, the ability of HSCs to sustain hematopoiesis over time, or their ability to reconstitute irradiated mice in primary or secondary transplants. Loss of N-cadherin does not lead to HSC depletion. N-cadherin expression by HSCs is not necessary for niche function.

| S-EPMC2681089 | biostudies-literature

NKAP Must Associate with HDAC3 to Regulate Hematopoietic Stem Cell Maintenance and Survival.

Project description:NKAP is a multifunctional nuclear protein that associates with the histone deacetylase HDAC3. Although both NKAP and HDAC3 are critical for hematopoietic stem cell (HSC) maintenance and survival, it was not known whether these two proteins work together. To assess the importance of their association in vivo, serial truncation and alanine scanning was performed on NKAP to identify the minimal binding site for HDAC3. Mutation of either Y352 or F347 to alanine abrogated the association of NKAP with HDAC3, but did not alter NKAP localization or expression. Using a linked conditional deletion/re-expression system in vivo, we demonstrated that re-expression of the Y352A NKAP mutant failed to restore HSC maintenance and survival in mice when endogenous NKAP expression was eliminated using Mx1-cre and poly-IC, whereas re-expression of wild type NKAP maintained the HSC pool. However, Y352A NKAP did restore proliferation in murine embryonic fibroblasts when endogenous NKAP expression was eliminated using ER-cre and tamoxifen. Therefore, Y352 in NKAP is critical for association with HDAC3 and for HSC maintenance and survival but is not important for proliferation of murine embryonic fibroblasts, demonstrating that NKAP functions in different complexes in different cell types.

| S-EPMC6456368 | biostudies-literature

Epitranscriptomic regulation of cortical neural stem cell maintenance via Mettl8-dependent mitochondrial tRNA m3C modification

Project description:Increasing evidence implicates critical roles of various epitranscriptomic RNA modifications in different biological processes. Methyltransferase METTL8 installs 3-methylcytosine modification of mitochondrial tRNAs in vitro, however, its role in intact biological systems is completely unknown. Here we show that Mettl8 is localized in the mitochondria and installs m3C in mitochondrial tRNASer(UCN)/Thr in mouse embryonic cortical neural stem cells. At molecular and cellular levels, Mettl8 deletion in cortical neural stem cells leads to reduced mitochondrial protein translation and attenuated respiration activity. At the functional level, conditional Mettl8 deletion in mice results in impaired embryonic cortical neural stem cell maintenance in vivo, which can be rescued by pharmacologically enhancing mitochondrial functions. Similarly, METTL8 regulates mitochondrial protein expression and neural stem cell maintenance in human forebrain cortical organoids. Together, our study reveals a conserved epitranscriptomic mechanism of Mettl8 and mitochondrial tRNA m3C modification in maintaining embryonic cortical neural stem cells in mice and humans.

2023-01-12 | GSE214445 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data