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Updated: Sep 30, 2025
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Assessment of Cellular Bioenergetics in Mouse Hematopoietic Stem and Primitive Progenitor Cells using the Extracellular Flux Analyzer
Published on: September 24, 2021
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Organelle dysfunction upon asrij depletion causes aging-like changes in mouse hematopoietic stem cells
Saloni Sinha1, Alice Sinha1, Prathamesh Dongre1
1Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
Aging Cell
|March 15, 2022
Summary
The protein Asrij/OCIAD1 prevents hematopoietic stem cell aging by maintaining organelle function. Restoring Asrij levels in aged cells improved mitochondrial and proteasome activity, crucial for blood system health.
Area of Science:
- Hematology
- Cellular Biology
- Aging Research
Background:
- Aging blood system shows increased hematopoietic stem cells (HSCs) and myeloid-biased differentiation, raising cancer risk.
- Asrij/OCIAD1 is vital for mammalian stem cell mitochondrial, endosomal, and proteasomal functions.
- Asrij deficiency mimics aged HSC traits like quiescence loss and DNA damage.
Purpose of the Study:
- To investigate Asrij's role in regulating organelle function within aged HSCs.
- To determine if Asrij levels decline with chronological aging in HSCs.
- To explore therapeutic potential of modulating Asrij for HSC aging.
Main Methods:
- Analysis of Asrij levels in aged wild-type (WT) HSCs.
- Transcriptome analysis of Asrij knockout (KO) HSCs.
- Assessment of organelle structure and function (mitochondria, endosomes, proteasomes) in Asrij KO mice.
- Pharmacological and lysophosphatidic acid-induced interventions in Asrij KO and aged WT mice.
Main Results:
- Aged WT HSCs exhibited reduced Asrij levels.
- Asrij KO HSCs showed mitochondrial damage, elevated ROS, impaired endosomal trafficking, and reduced proteasome activity.
- Pharmacological correction of organelles in Asrij KO mice restored HSC and myeloid cell frequencies.
- Lysophosphatidic acid treatment upregulated Asrij in aged WT mice, rescuing organelle function and HSC frequency.
Conclusions:
- Asrij/OCIAD1 is crucial for preventing HSC aging by maintaining organelle homeostasis.
- Declining Asrij levels contribute to HSC aging phenotypes.
- Targeting Asrij or its associated organelle functions offers a potential strategy for combating HSC aging and related diseases.
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