An X chromosome gene regulates hematopoietic stem cell kinetics
Females are natural mosaics for X chromosome-linked genes. As X chromosome inactivation occurs randomly, the ratio of parental phenotypes among blood cells is approximately 1:1. Recently, however, ratios of greater than 3:1 have been observed in 38-56% of women over age 60. This could result from a depletion of hematopoietic stem cells (HSCs) with aging (and the maintenance of hematopoiesis by a few residual clones) or from myelodysplasia (the dominance of a neoplastic clone). Each possibility has major implications for chemotherapy and for transplantation in elderly patients. We report similar findings in longitudinal studies of female Safari cats and demonstrate that the excessive skewing that develops with aging results from a third mechanism that has no pathologic consequence, hemizygous selection. We show that there is a competitive advantage for all HSCs with a specific X chromosome phenotype and, thus, demonstrate that an X chromosome gene (or genes) regulates HSC replication, differentiation, and/or survival.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1998 |
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| Erschienen: |
1998 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:95 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 95(1998), 7 vom: 31. März, Seite 3862-6 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Abkowitz, J L [VerfasserIn] |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 01.05.1998 Date Revised 14.02.2024 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM094619964 |
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| 100 | 1 | |a Abkowitz, J L |e verfasserin |4 aut | |
| 245 | 1 | 3 | |a An X chromosome gene regulates hematopoietic stem cell kinetics |
| 264 | 1 | |c 1998 | |
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| 500 | |a Date Completed 01.05.1998 | ||
| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Females are natural mosaics for X chromosome-linked genes. As X chromosome inactivation occurs randomly, the ratio of parental phenotypes among blood cells is approximately 1:1. Recently, however, ratios of greater than 3:1 have been observed in 38-56% of women over age 60. This could result from a depletion of hematopoietic stem cells (HSCs) with aging (and the maintenance of hematopoiesis by a few residual clones) or from myelodysplasia (the dominance of a neoplastic clone). Each possibility has major implications for chemotherapy and for transplantation in elderly patients. We report similar findings in longitudinal studies of female Safari cats and demonstrate that the excessive skewing that develops with aging results from a third mechanism that has no pathologic consequence, hemizygous selection. We show that there is a competitive advantage for all HSCs with a specific X chromosome phenotype and, thus, demonstrate that an X chromosome gene (or genes) regulates HSC replication, differentiation, and/or survival | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 700 | 1 | |a Taboada, M |e verfasserin |4 aut | |
| 700 | 1 | |a Shelton, G H |e verfasserin |4 aut | |
| 700 | 1 | |a Catlin, S N |e verfasserin |4 aut | |
| 700 | 1 | |a Guttorp, P |e verfasserin |4 aut | |
| 700 | 1 | |a Kiklevich, J V |e verfasserin |4 aut | |
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