U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

SRX22643571: GSM7918295: IR_1; Homo sapiens; RNA-Seq
1 ILLUMINA (Illumina NovaSeq 6000) run: 39.9M spots, 12G bases, 3.9Gb downloads

External Id: GSM7918295_r1
Submitted by: Institute of Life Sciences, Chongqing Medical University
Study: Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening (human_HSC_RNA_Seq)
show Abstracthide Abstract
Mitochondria have recently been identified as a critical regulator for the homeostasis of hematopoietic stem cells (HSCs). However, the mechanism underlying HSC regulation still needs to be clarified. Here, we identify transcription factor Nynrin as a novel regulator of HSC maintenance through modulation of mitochondrial function. We demonstrate that Nynrin is highly expressed in HSC under steady and stress state. Nynrin knockout leads to significantly decreased long-term HSC frequency, markedly reduced HSC dormancy, and self-renewal capacity in steady-state and stress hematopoiesis. We observed abnormal mitochondrial metabolism and mitochondrial permeability transition pore (mPTP) opening in Nynrin-deficient HSCs. Notably, Nynrin-deficient HSCs are more compromised in tolerance of irradiation- and 5-fluorouracil-induced stresses and exhibit typical phenotypes of necrosis. In contrast, overexpression of Nynrin in HSC is resistant to the radiation. Mechanistically, Nynrin deletion induces transactivation of Ppif. Overexpression of cyclophilin D (CypD), the protein encoded by the Ppif gene, causes mPTP opening, mitochondrial swelling, ROS overinduction, and cell necrosis. Both blocking the function of CypD by using cyclosporin A (CsA) or reducing the expression of Ppif could inhibit Nynrin deficiency-induced mitochondrial metabolism enhancement and ROS overproduction, thereby evidently rescuing the impairment of HSCs in Nynrin mutant mice. Collectively, our data, for the first time, characterize Nynrin as a critical regulator of HSC function acting through the Ppif/mPTP mitochondria axis and highlight the importance of Nynrin in HSC maintenance. These data provide new insights into the mechanisms for controlling HSC fate.? Overall design: CD34+ cells were enriched from total bone marrow cells accroding to EasySep™ Human Progenitor Cell Enrichment Kit II. TheCD34+ cells werewere irradiated with 2Gy ?-rays. We then performed gene expression profiling analysis using data obtained from RNA-seq of human CD34+ Comparative gene expression profiling analysis of RNA-seq data for nonirradiated CD34+ and irradiated CD34+
Sample: IR_1
SAMN38440419 • SRS19640945 • All experiments • All runs
Organism: Homo sapiens
Library:
Name: GSM7918295
Instrument: Illumina NovaSeq 6000
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: PAIRED
Construction protocol: RNA was harvested using TRIzol™ LS Reagent(invitrogen).All the RNA was used for the construction of sequencing libraries. RNA libraries for RNA-seq were prepared using TruePrepTM DNA Library Prep Kit V2 for Illumina® and TruePrepTM Index Kit V2/V3 for Illumina® (vazyme).
Runs: 1 run, 39.9M spots, 12G bases, 3.9Gb
Run# of Spots# of BasesSizePublished
SRR2694981139,911,98212G3.9Gb2024-06-01

ID:
30656270

Supplemental Content

Search details

See more...

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...