Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells

被引：70

作者：

Grinenko, Tatyana ^{[1
]}

Arndt, Kathrin ^{[1
]}

Portz, Melanie ^{[1
]}

Mende, Nicole ^{[1
]}

Guenther, Marko ^{[1
]}

Cosgun, Kadriye Nehir ^{[1
]}

Alexopoulou, Dimitra ^{[2
]}

Lakshmanaperumal, Naharajan ^{[3
]}

Henry, Ian ^{[3
]}

Dahl, Andreas ^{[2
]}

Waskow, Claudia ^{[1
]}

机构：

[1] Tech Univ Dresden, Ctr Regenerat Therapies Dresden, Regenerat Hematopoiesis Lab, D-01307 Dresden, Germany

[2] Tech Univ Dresden, Ctr Biotechnol, Deep Sequencing Grp SFB 655, D-01307 Dresden, Germany

[3] Max Planck Inst Mol Cell Biol & Genet, Bioinformat Serv, D-01307 Dresden, Germany

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2014年 / 211卷 / 02期

关键词：

C-KIT; EXPRESSION; HETEROGENEITY; MOUSE; TRANSPLANTATION; MAINTENANCE;

D O I：

10.1084/jem.20131115

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：209 / 215

页数：7

共 27 条

[1] Differential expression analysis for sequence count data [J].