Analysis of Gene Expression Profiles of Hematopoietic Stem and Progenitor Cells Exposed
to Continuous Low dose-rate Gamma-rays
Tokuhisa HIROUCHI, Satoshi TANAKA, Ignacia TANAKA, Jun-ichiro KOMURA
Department of Radiobiology
Abstract
We have previously shown that continuous exposure to low dose-rate (LDR) radiation is leukemogenic
in mice. In this study, we investigated how LDR radiation changes cell numbers and gene expressions ofimmature hematopoietic cells, involving stem cells (HSCs) and three kinds of progenitor cells (HPCs). Miceirradiated with LDR (20mGy/day) γ-rays for 400 days were subjected to FACS and gene expression analysis,
and the analysis results were compared with those of age-matched non-irradiated control mice. HSCs andHPCs in irradiated mice were decreased during and after the irradiation, but manners of the cell decreases
showed different patterns. Although HSC decreases were the most prominent and prolonged, annotations ofgene expression profiles of HSCs during and after the irradiation suggested that bio-functions associatedwith “cell survival” and “cell viability” were frequently promoted, and that “cell death”- and“apoptosis”-related bio-functions were suppressed. Annotation analyses of gene expression profiles of HPCs
resulted similar trends. The similarities among HSCs and HPCs were more clearly found after 300-day
irradiation, such that many transcription factors and biological networks predicted to be important for
responding LDR radiation were identical among HSCs and HPCs at days 300 and 400. These results suggest
unique LDR radiation-induced responses in immature hematopoietic cells.

多能性前駆細胞

Cell number (x105)
6.0
6.0E+053.0
3.0E+054.0
4.0E+052.0
2.0E+052.0
2.0E+051.0
1.0E+05

100



 **
 **
**
 **
 **

200

300

400

500

600

**
300



400

500

リ ン パ球系共通前駆細胞

骨髄球系共通前駆細胞
3.0
3.0E+061.5

1.5E+062.0
2.0E+061.0
1.0E+06
0.0E+000
0200

Days after the start of irradiation

2.0
2.0E+060.5
5.0E+05
100

Days after the start of irradiation

2.5
2.5E+06Cell number (x106)


0.0E+000
0

Cell number (x106)



0.0E+000
0

Cell number (x105)


造血幹細胞
4.0E+05
4.0


1.0

1.0E+06

**

 **
**


100200300


**
600

**

400

500

Days after the start of irradiation

600
0.0E+000
0**

100200300


**
400

500

600

Days after the start of irradiation

Fig. 1

Alterations in number of hematopoietic stem cells (HSCs) and three kinds ofhematopoietic progenitor cells (HPCs) during and after irradiation of B6C3F1 malemice with γ-rays at a dose rate of 20 mGy/day for 400 days from 8 weeks of age. Bonemarrow cells were obtained at a 100-day interval, and hematopoietic stem cells (A),multi-potent progenitor cells (B), common lymphoid progenitor cells (C) and common
myeloid progenitor cells (D) were counted. Closed and open circles indicate values of
non-irradiated mice and irradiated mice, respectively. Bars represent standard deviation.
(*:p<0.05, **:p<0.01, t test)

Table 1A part of the analysis of the gene expression profiles of hematopoietic stem cells(HSCs) in B6C3F1 male mice exposed to γ-rays at a dose rate of 20 mGy /day for 200
days from 8 weeks of age. Only cell death- or survival-related bio-functions are listed
here. The activation z-scores of the bio-functions were calculated from expression
profiles of top 1%, 2%, 4%, 8% or 10% of the total analyzed genes; positive z-scores
predict promotion; negative z-scores predict suppression.