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Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells
Long-term hematopoietic stem cells (HSCs [LT-HSCs]) are well known to display unpredictable differences in their clonal expansion capacities after transplantation. Here, by analyzing the cellular output after transplantation of stem cells differing in surface expression levels of the Kit receptor, w...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920556/ https://www.ncbi.nlm.nih.gov/pubmed/24446490 http://dx.doi.org/10.1084/jem.20131115 |
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author | Grinenko, Tatyana Arndt, Kathrin Portz, Melanie Mende, Nicole Günther, Marko Cosgun, Kadriye Nehir Alexopoulou, Dimitra Lakshmanaperumal, Naharajan Henry, Ian Dahl, Andreas Waskow, Claudia |
author_facet | Grinenko, Tatyana Arndt, Kathrin Portz, Melanie Mende, Nicole Günther, Marko Cosgun, Kadriye Nehir Alexopoulou, Dimitra Lakshmanaperumal, Naharajan Henry, Ian Dahl, Andreas Waskow, Claudia |
author_sort | Grinenko, Tatyana |
collection | PubMed |
description | Long-term hematopoietic stem cells (HSCs [LT-HSCs]) are well known to display unpredictable differences in their clonal expansion capacities after transplantation. Here, by analyzing the cellular output after transplantation of stem cells differing in surface expression levels of the Kit receptor, we show that LT-HSCs can be systematically subdivided into two subtypes with distinct reconstitution behavior. LT-HSCs expressing intermediate levels of Kit receptor (Kit(int)) are quiescent in situ but proliferate extensively after transplantation and therefore repopulate large parts of the recipient’s hematopoietic system. In contrast, metabolically active Kit(hi) LT-HSCs display more limited expansion capacities and show reduced but robust levels of repopulation after transfer. Transplantation into secondary and tertiary recipient mice show maintenance of efficient repopulation capacities of Kit(int) but not of Kit(hi) LT-HSCs. Initiation of differentiation is marked by the transit from Kit(int) to Kit(hi) HSCs, both of which precede any other known stem cell population. |
format | Online Article Text |
id | pubmed-3920556 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-39205562014-08-10 Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells Grinenko, Tatyana Arndt, Kathrin Portz, Melanie Mende, Nicole Günther, Marko Cosgun, Kadriye Nehir Alexopoulou, Dimitra Lakshmanaperumal, Naharajan Henry, Ian Dahl, Andreas Waskow, Claudia J Exp Med Brief Definitive Report Long-term hematopoietic stem cells (HSCs [LT-HSCs]) are well known to display unpredictable differences in their clonal expansion capacities after transplantation. Here, by analyzing the cellular output after transplantation of stem cells differing in surface expression levels of the Kit receptor, we show that LT-HSCs can be systematically subdivided into two subtypes with distinct reconstitution behavior. LT-HSCs expressing intermediate levels of Kit receptor (Kit(int)) are quiescent in situ but proliferate extensively after transplantation and therefore repopulate large parts of the recipient’s hematopoietic system. In contrast, metabolically active Kit(hi) LT-HSCs display more limited expansion capacities and show reduced but robust levels of repopulation after transfer. Transplantation into secondary and tertiary recipient mice show maintenance of efficient repopulation capacities of Kit(int) but not of Kit(hi) LT-HSCs. Initiation of differentiation is marked by the transit from Kit(int) to Kit(hi) HSCs, both of which precede any other known stem cell population. The Rockefeller University Press 2014-02-10 /pmc/articles/PMC3920556/ /pubmed/24446490 http://dx.doi.org/10.1084/jem.20131115 Text en © 2014 Grinenko et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Grinenko, Tatyana Arndt, Kathrin Portz, Melanie Mende, Nicole Günther, Marko Cosgun, Kadriye Nehir Alexopoulou, Dimitra Lakshmanaperumal, Naharajan Henry, Ian Dahl, Andreas Waskow, Claudia Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells |
title | Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells |
title_full | Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells |
title_fullStr | Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells |
title_full_unstemmed | Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells |
title_short | Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells |
title_sort | clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920556/ https://www.ncbi.nlm.nih.gov/pubmed/24446490 http://dx.doi.org/10.1084/jem.20131115 |
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