Nardilysin determines hematopoietic stem cell fitness by regulating protein synthesis.

Shinichiro Oshima, Rahul Sinha, Mikiko Ohno, Kiyoto Nishi, Koji Eto, Akifumi Takaori-Kondo, Eiichiro Nishi, Ryo Yamamoto

Biochemical and biophysical research communications 2024 Jan 22

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Nardilysin (NRDC) is a multifunctional protein required for maintaining homeostasis in various cellular and tissue contexts. However, its role in hematopoietic stem cells (HSCs) remains unclear. Here, through the conditional deletion of NRDC in hematopoietic cells, we demonstrate that NRDC is required for HSCs expansion in vitro and the reconstitution of hematopoiesis in vivo after transplantation. We found NRDC-deficient HSCs lose their self-renewal ability and display a preferential bias to myeloid differentiation in response to replication stress. Transcriptome data analysis revealed the upregulation of heat shock response-related genes in NRDC-deficient HSCs. Additionally, we observed increased protein synthesis in cultured NRDC-deficient HSCs. Thus, loss of NRDC may cause the inability to control protein synthesis in response to replication induced protein stress, leading to the impaired HSC self-renewal ability. This highlights a novel model of action of NRDC specifically in HSCs. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Shinichiro Oshima, Rahul Sinha, Mikiko Ohno, Kiyoto Nishi, Koji Eto, Akifumi Takaori-Kondo, Eiichiro Nishi, Ryo Yamamoto. Nardilysin determines hematopoietic stem cell fitness by regulating protein synthesis. Biochemical and biophysical research communications. 2024 Jan 22;693:149355