NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE248638 Query DataSets for GSE248638
Status Public on Jun 01, 2024
Title Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening (scRNA-Seq)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
Nynrin gene may play an important role in hematopoietic reconstitution.We used single cell RNA sequencing (scRNA-seq) to analyze the expression of nynrin in hemopoietic progenitor cell.
 
Overall design Lin- cells were enriched from C57/B6 mice according to the EasySep™ Mouse Hematopoietic Progenitor Cell Isolation Kit.Lin- cells were analyed using scRNA-seq.
 
Contributor(s) Zhou C, Kuang M, Hou Y
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Nov 26, 2023
Last update date Jun 01, 2024
Contact name CHENGFANG ZHOU
E-mail(s) chengfangzhou47@gmail.com
Phone (86)13368348471
Organization name Chongqing Medical University
Department Institute of Life Sciences
Street address No. 1, Medical College Road
City Chongqing
ZIP/Postal code 400032
Country China
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (1)
GSM7918306 Lin- cells_scRNA-seq
This SubSeries is part of SuperSeries:
GSE248639 Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening.
Relations
BioProject PRJNA1045295

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE248638_RAW.tar 590.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap