Variable SATB1 Levels Regulate Hematopoietic Stem Cell Heterogeneity with Distinct Lineage Fate

被引：32

作者：

Doi, Yukiko ^{[1
]}

Yokota, Takafumi ^{[1
]}

Satoh, Yusuke ^{[1
,2
]}

Okuzaki, Daisuke ^{[3
]}

Tokunaga, Masahiro ^{[1
]}

Ishibashi, Tomohiko ^{[1
,4
]}

Sudo, Takao ^{[1
,5
]}

Ueda, Tomoaki ^{[1
]}

Shingai, Yasuhiro ^{[1
]}

Ichii, Michiko ^{[1
]}

Tanimura, Akira ^{[1
]}

Ezoe, Sachiko ^{[1
]}

Shibayama, Hirohiko ^{[1
]}

Kohwi-Shigematsu, Terumi ^{[6
]}

Takeda, Junji ^{[7
]}

Oritani, Kenji ^{[1
]}

Kanakura, Yuzuru ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Hematol & Oncol, Suita, Osaka, Japan

[2] Kobe Shoin Womens Univ, Dept Lifestyle Studies, Kobe, Hyogo, Japan

[3] Osaka Univ, DNA Chip Dev Ctr Infect Dis, Res Inst Microbial Dis, Suita, Osaka, Japan

[4] Natl Cerebral & Cardiovasc Ctr Res Inst, Dept Vasc Physiol, Suita, Osaka, Japan

[5] Osaka Univ, Dept Immunol & Cell Biol, Grad Sch Med, Suita, Osaka, Japan

[6] Univ Calif San Francisco, Dept Orofacial Sci, San Francisco, CA 94143 USA

[7] Osaka Univ, Grad Sch Med, Dept Genome Biol, Suita, Osaka, Japan

来源：

CELL REPORTS | 2018年 / 23卷 / 11期

基金：

日本学术振兴会;

关键词：

BONE-MARROW; SELF-RENEWAL; PROGENITORS; IDENTIFICATION; COMMITMENT; EXPRESSION; MARKS; DIFFERENTIATION; TRANSCRIPTION; COMPARTMENT;

D O I：

10.1016/j.celrep.2018.05.042

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Hematopoietic stem cells (HSCs) comprise a heterogeneous population exhibiting self-renewal and differentiation capabilities; however, the mechanisms involved in maintaining this heterogeneity remain unclear. Here, we show that SATB1 is involved in regulating HSC heterogeneity. Results in conditional Satb1-knockout mice revealed that SATB1 was important for the self-renewal and lymphopoiesis of adult HSCs. Additionally, HSCs from Satb1/Tomato-knockin reporter mice were classified based on SATB1/Tomato intensity, with transplantation experiments revealing stronger differentiation toward the lymphocytic lineage along with high SATB1 levels, whereas SATB1(-) HSCs followed the myeloid lineage in agreement with genome-wide transcription and cell culture studies. Importantly, SATB1(-) and SATB1(+) HSC populations were interconvertible upon transplantation, with SATB1(+) HSCs showing higher reconstituting and lymphopoietic potentials in primary recipients relative to SATB1(-) HSCs, whereas both HSCs exhibited equally efficient reconstituted lym-pho-hematopoiesis in secondary recipients. These results suggest that SATB1 levels regulate the maintenance of HSC multipotency, with variations contributing to HSC heterogeneity.

引用

页码：3223 / 3235

页数：13

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