An iron rheostat controls hematopoietic stem cell fate
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved..
Mechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response to limited iron-particularly during mitosis. To study the functional and molecular consequences of iron restriction, we developed models allowing for transient iron bioavailability limitation and combined single-molecule RNA quantification, metabolomics, and single-cell transcriptomic analyses with functional studies. Our data reveal that the activation of the limited iron response triggers coordinated metabolic and epigenetic events, establishing stemness-conferring gene regulation. Notably, we find that aging-associated cytoplasmic iron loading reversibly attenuates iron-dependent cell fate control, explicating intervention strategies for dysfunctional aged stem cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Cell stem cell - 31(2024), 3 vom: 07. März, Seite 378-397.e12 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kao, Yun-Ruei [VerfasserIn] |
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| Links: |
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| Themen: |
Aging |
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| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.stem.2024.01.011 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 3 | |a An iron rheostat controls hematopoietic stem cell fate |
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| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Mechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response to limited iron-particularly during mitosis. To study the functional and molecular consequences of iron restriction, we developed models allowing for transient iron bioavailability limitation and combined single-molecule RNA quantification, metabolomics, and single-cell transcriptomic analyses with functional studies. Our data reveal that the activation of the limited iron response triggers coordinated metabolic and epigenetic events, establishing stemness-conferring gene regulation. Notably, we find that aging-associated cytoplasmic iron loading reversibly attenuates iron-dependent cell fate control, explicating intervention strategies for dysfunctional aged stem cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Tip60/KAT5 | |
| 650 | 4 | |a aging | |
| 650 | 4 | |a gene regulation | |
| 650 | 4 | |a hematopoiesis | |
| 650 | 4 | |a iron | |
| 650 | 4 | |a metabolism | |
| 650 | 4 | |a stem cells | |
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| 700 | 1 | |a Chen, Jiahao |e verfasserin |4 aut | |
| 700 | 1 | |a Kumari, Rajni |e verfasserin |4 aut | |
| 700 | 1 | |a Ng, Anita |e verfasserin |4 aut | |
| 700 | 1 | |a Zintiridou, Aliona |e verfasserin |4 aut | |
| 700 | 1 | |a Tatiparthy, Madhuri |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Yuhong |e verfasserin |4 aut | |
| 700 | 1 | |a Aivalioti, Maria M |e verfasserin |4 aut | |
| 700 | 1 | |a Moulik, Deeposree |e verfasserin |4 aut | |
| 700 | 1 | |a Sundaravel, Sriram |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Daqian |e verfasserin |4 aut | |
| 700 | 1 | |a Reisz, Julie A |e verfasserin |4 aut | |
| 700 | 1 | |a Grimm, Juliane |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez-Lopez, Nuria |e verfasserin |4 aut | |
| 700 | 1 | |a Stransky, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Sidoli, Simone |e verfasserin |4 aut | |
| 700 | 1 | |a Steidl, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Rajat |e verfasserin |4 aut | |
| 700 | 1 | |a D'Alessandro, Angelo |e verfasserin |4 aut | |
| 700 | 1 | |a Will, Britta |e verfasserin |4 aut | |
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