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Hematopoietic stem cells count and remember self-renewal divisions

Hematopoietic stem cells count and remember self-renewal divisions
Hematopoietic stem cells count and remember self-renewal divisions
The ability of cells to count and remember their divisions could underlie many alterations that occur during development, aging, and disease. We tracked the cumulative divisional history of slow-cycling hematopoietic stem cells (HSCs) throughout adult life. This revealed a fraction of rarely dividing HSCs that contained all the long-term HSC (LT-HSC) activity within the aging HSC compartment. During adult life, this population asynchronously completes four traceable symmetric self-renewal divisions to expand its size before entering a state of dormancy. We show that the mechanism of expansion involves progressively lengthening periods between cell divisions, with long-term regenerative potential lost upon a fifth division. Our data also show that age-related phenotypic changes within the HSC compartment are divisional history dependent. These results suggest that HSCs accumulate discrete memory stages over their divisional history and provide evidence for the role of cellular memory in HSC aging.
0092-8674
1296-1309
Bernitz, Jeffrey
ff273a33-7896-4938-91b9-e86165bdbb81
Kim, Huen Suk
e146d02e-25f7-4e9b-ad51-49f4cc09afe3
Macarthur, Benjamin
2c0476e7-5d3e-4064-81bb-104e8e88bb6b
Sieburg, Hans
e954ce8c-b416-4768-9395-d7ab723d7a8d
Moore, Kateri
27387f4d-f7e3-4cbb-b506-788d2f4b4ac0
Bernitz, Jeffrey
ff273a33-7896-4938-91b9-e86165bdbb81
Kim, Huen Suk
e146d02e-25f7-4e9b-ad51-49f4cc09afe3
Macarthur, Benjamin
2c0476e7-5d3e-4064-81bb-104e8e88bb6b
Sieburg, Hans
e954ce8c-b416-4768-9395-d7ab723d7a8d
Moore, Kateri
27387f4d-f7e3-4cbb-b506-788d2f4b4ac0

Bernitz, Jeffrey, Kim, Huen Suk, Macarthur, Benjamin, Sieburg, Hans and Moore, Kateri (2016) Hematopoietic stem cells count and remember self-renewal divisions. Cell, 167 (5), 1296-1309. (doi:10.1016/j.cell.2016.10.022). (PMID:27839867)

Record type: Article

Abstract

The ability of cells to count and remember their divisions could underlie many alterations that occur during development, aging, and disease. We tracked the cumulative divisional history of slow-cycling hematopoietic stem cells (HSCs) throughout adult life. This revealed a fraction of rarely dividing HSCs that contained all the long-term HSC (LT-HSC) activity within the aging HSC compartment. During adult life, this population asynchronously completes four traceable symmetric self-renewal divisions to expand its size before entering a state of dormancy. We show that the mechanism of expansion involves progressively lengthening periods between cell divisions, with long-term regenerative potential lost upon a fifth division. Our data also show that age-related phenotypic changes within the HSC compartment are divisional history dependent. These results suggest that HSCs accumulate discrete memory stages over their divisional history and provide evidence for the role of cellular memory in HSC aging.

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Accepted/In Press date: 12 October 2016
e-pub ahead of print date: 10 November 2016
Published date: 17 November 2016
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 404458
URI: http://eprints.soton.ac.uk/id/eprint/404458
ISSN: 0092-8674
PURE UUID: 7c0d198b-fc06-4144-90b6-a62e00e83445

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Date deposited: 10 Jan 2017 13:59
Last modified: 08 May 2020 04:01

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Contributors

Author: Jeffrey Bernitz
Author: Huen Suk Kim
Author: Hans Sieburg
Author: Kateri Moore

University divisions

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