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Lysosomes and Their Role in Regulating the Metabolism of Hematopoietic Stem Cells

SIMPLE SUMMARY: Hematopoietic stem cells (HSCs) are an essential component of the cellular architecture of the body. These cells are responsible for self-renewal as well as the production of hematopoietic progenitors and adult blood cells. HSCs have been successfully used as a treatment for a variet...

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Autor principal: Arif, Tasleem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598322/
https://www.ncbi.nlm.nih.gov/pubmed/36290314
http://dx.doi.org/10.3390/biology11101410
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author Arif, Tasleem
author_facet Arif, Tasleem
author_sort Arif, Tasleem
collection PubMed
description SIMPLE SUMMARY: Hematopoietic stem cells (HSCs) are an essential component of the cellular architecture of the body. These cells are responsible for self-renewal as well as the production of hematopoietic progenitors and adult blood cells. HSCs have been successfully used as a treatment for a variety of hematological disorders, including lymphoma, leukemia, anemia, and anomalies in the immune system. However, owing to the difficulties associated with the limited supply of HSCs, the majority of hematological conditions cannot be treated in clinical settings. It is possible that understanding the intrinsic and extrinsic regulators of HSC stemness could pave the way for developing novel methods for accessing alternative HSC sources. This would enable researchers to get around the limitations that currently exist in clinical applications. ABSTRACT: Hematopoietic stem cells (HSCs) have the capacity to renew blood cells at all stages of life and are largely quiescent at a steady state. It is essential to understand the processes that govern quiescence in HSCs to enhance bone marrow transplantation. It is hypothesized that in their quiescent state, HSCs primarily use glycolysis for energy production rather than mitochondrial oxidative phosphorylation (OXPHOS). In addition, the HSC switch from quiescence to activation occurs along a continuous developmental path that is driven by metabolism. Specifying the metabolic regulation pathway of HSC quiescence will provide insights into HSC homeostasis for therapeutic application. Therefore, understanding the metabolic demands of HSCs at a steady state is key to developing innovative hematological therapeutics. Lysosomes are the major degradative organelle in eukaryotic cells. Catabolic, anabolic, and lysosomal function abnormalities are connected to an expanding list of diseases. In recent years, lysosomes have emerged as control centers of cellular metabolism, particularly in HSC quiescence, and essential regulators of cell signaling have been found on the lysosomal membrane. In addition to autophagic processes, lysosomal activities have been shown to be crucial in sustaining quiescence by restricting HSCs access to a nutritional reserve essential for their activation into the cell cycle. Lysosomal activity may preserve HSC quiescence by altering glycolysis-mitochondrial biogenesis. The understanding of HSC metabolism has significantly expanded over the decade, revealing previously unknown requirements of HSCs in both their dividing (active) and quiescent states. Therefore, understanding the role of lysosomes in HSCs will allow for the development of innovative treatment methods based on HSCs to fight clonal hematopoiesis and HSC aging.
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spelling pubmed-95983222022-10-27 Lysosomes and Their Role in Regulating the Metabolism of Hematopoietic Stem Cells Arif, Tasleem Biology (Basel) Review SIMPLE SUMMARY: Hematopoietic stem cells (HSCs) are an essential component of the cellular architecture of the body. These cells are responsible for self-renewal as well as the production of hematopoietic progenitors and adult blood cells. HSCs have been successfully used as a treatment for a variety of hematological disorders, including lymphoma, leukemia, anemia, and anomalies in the immune system. However, owing to the difficulties associated with the limited supply of HSCs, the majority of hematological conditions cannot be treated in clinical settings. It is possible that understanding the intrinsic and extrinsic regulators of HSC stemness could pave the way for developing novel methods for accessing alternative HSC sources. This would enable researchers to get around the limitations that currently exist in clinical applications. ABSTRACT: Hematopoietic stem cells (HSCs) have the capacity to renew blood cells at all stages of life and are largely quiescent at a steady state. It is essential to understand the processes that govern quiescence in HSCs to enhance bone marrow transplantation. It is hypothesized that in their quiescent state, HSCs primarily use glycolysis for energy production rather than mitochondrial oxidative phosphorylation (OXPHOS). In addition, the HSC switch from quiescence to activation occurs along a continuous developmental path that is driven by metabolism. Specifying the metabolic regulation pathway of HSC quiescence will provide insights into HSC homeostasis for therapeutic application. Therefore, understanding the metabolic demands of HSCs at a steady state is key to developing innovative hematological therapeutics. Lysosomes are the major degradative organelle in eukaryotic cells. Catabolic, anabolic, and lysosomal function abnormalities are connected to an expanding list of diseases. In recent years, lysosomes have emerged as control centers of cellular metabolism, particularly in HSC quiescence, and essential regulators of cell signaling have been found on the lysosomal membrane. In addition to autophagic processes, lysosomal activities have been shown to be crucial in sustaining quiescence by restricting HSCs access to a nutritional reserve essential for their activation into the cell cycle. Lysosomal activity may preserve HSC quiescence by altering glycolysis-mitochondrial biogenesis. The understanding of HSC metabolism has significantly expanded over the decade, revealing previously unknown requirements of HSCs in both their dividing (active) and quiescent states. Therefore, understanding the role of lysosomes in HSCs will allow for the development of innovative treatment methods based on HSCs to fight clonal hematopoiesis and HSC aging. MDPI 2022-09-27 /pmc/articles/PMC9598322/ /pubmed/36290314 http://dx.doi.org/10.3390/biology11101410 Text en © 2022 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Arif, Tasleem
Lysosomes and Their Role in Regulating the Metabolism of Hematopoietic Stem Cells
title Lysosomes and Their Role in Regulating the Metabolism of Hematopoietic Stem Cells
title_full Lysosomes and Their Role in Regulating the Metabolism of Hematopoietic Stem Cells
title_fullStr Lysosomes and Their Role in Regulating the Metabolism of Hematopoietic Stem Cells
title_full_unstemmed Lysosomes and Their Role in Regulating the Metabolism of Hematopoietic Stem Cells
title_short Lysosomes and Their Role in Regulating the Metabolism of Hematopoietic Stem Cells
title_sort lysosomes and their role in regulating the metabolism of hematopoietic stem cells
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598322/
https://www.ncbi.nlm.nih.gov/pubmed/36290314
http://dx.doi.org/10.3390/biology11101410
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