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

共 30 条

[21] CD86 is expressed on murine hematopoietic stem cells and denotes lymphopoietic potential [J].

Shimazu, Tomoyuki ;

Iida, Ryuji ;

Zhang, Qingzhao ;

Welner, Robert S. ;

Medina, Kay L. ;

Alberola-Ila, Jose ;

Kincade, Paul W. .

BLOOD, 2012, 119 (21) :4889-4897

[22] Required enhancer-matrin-3 network interactions for a homeodomain transcription program [J].

Skowronska-Krawczyk, Dorota ;

Ma, Qi ;

Schwartz, Michal ;

Scully, Kathleen ;

Li, Wenbo ;

Liu, Zhijie ;

Taylor, Havilah ;

Tollkuhn, Jessica ;

Ohgi, Kenneth A. ;

Notani, Dimple ;

Kohwi, Yoshinori ;

Kohwi-Shigematsu, Terumi ;

Rosenfeld, Michael G. .

NATURE, 2014, 514 (7521) :257-+

[23] Human haematopoietic stem cell lineage commitment is a continuous process [J].

Velten, Lars ;

Haas, Simon F. ;

Raffel, Simon ;

Blaszkiewicz, Sandra ;

Islam, Saiful ;

Hennig, Bianca P. ;

Hirche, Christoph ;

Lutz, Christoph ;

Buss, Eike C. ;

Nowak, Daniel ;

Boch, Tobias ;

Hofmann, Wolf-Karsten ;

Ho, Anthony D. ;

Huber, Wolfgang ;

Trumpp, Andreas ;

Essers, Marieke A. G. ;

Steinmetz, Lars M. .

NATURE CELL BIOLOGY, 2017, 19 (04) :271-+

[24] Satb1 regulates the self-renewal of hematopoietic stem cells by promoting quiescence and repressing differentiation commitment [J].

Will, Britta ;

Vogler, Thomas O. ;

Bartholdy, Boris ;

Garrett-Bakelman, Francine ;

Mayer, Jillian ;

Barreyro, Laura ;

Pandolfi, Ashley ;

Todorova, Tihomira I. ;

Okoye-Okafor, Ujunwa C. ;

Stanley, Robert F. ;

Bhagat, Tushar D. ;

Verma, Amit ;

Figueroa, Maria E. ;

Melnick, Ari ;

Roth, Michael ;

Steidl, Ulrich .

NATURE IMMUNOLOGY, 2013, 14 (05) :437-+

[25] Hematopoietic Stem Cells Reversibly Switch from Dormancy to Self-Renewal during Homeostasis and Repair [J].

Wilson, Anne ;

Laurenti, Elisa ;

Oser, Gabriela ;

van der Wath, Richard C. ;

Blanco-Bose, William ;

Jaworski, Maike ;

Offner, Sandra ;

Dunant, Cyrille F. ;

Eshkind, Leonid ;

Bockamp, Ernesto ;

Lio, Pietro ;

MacDonald, H. Robson ;

Trumpp, Andreas .

CELL, 2008, 135 (06) :1118-1129

[26] Clonal Analysis Unveils Self-Renewing Lineage-Restricted Progenitors Generated Directly from Hematopoietic Stem Cells [J].

Yamamoto, Ryo ;

Morita, Yohei ;

Ooehara, Jun ;

Hamanaka, Sanae ;

Onodera, Masafumi ;

Rudolph, Karl Lenhard ;

Ema, Hideo ;

Nakauchi, Hiromitsu .

CELL, 2013, 154 (05) :1112-1126

[27] Unique properties of fetal lymphoid progenitors identified according to RAG1 gene expression [J].

Yokota, T ;

Kouro, T ;

Hirose, J ;

Igarashi, H ;

Garrett, KP ;

Gregory, SC ;

Sakaguchi, N ;

Owen, JJT ;

Kincade, PW .

IMMUNITY, 2003, 19 (03) :365-375

[28] Soluble Frizzled-Related Protein 1 Is Estrogen Inducible in Bone Marrow Stromal Cells and Suppresses the Earliest Events in Lymphopoiesis [J].

Yokota, Takafumi ;

Oritani, Kenji ;

Garrett, Karla P. ;

Kouro, Taku ;

Nishida, Makoto ;

Takahashi, Isao ;

Ichii, Michiko ;

Satoh, Yusuke ;

Kincade, Paul W. ;

Kanakura, Yuzuru .

JOURNAL OF IMMUNOLOGY, 2008, 181 (09) :6061-6072

[29] The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice [J].

Yokota, Takafumi ;

Oritani, Kenji ;

Butz, Stefan ;

Kokame, Koichi ;

Kincade, Paul W. ;

Miyata, Toshiyuki ;

Vestweber, Dietmar ;

Kanakura, Yuzuru .

BLOOD, 2009, 113 (13) :2914-2923

[30] Epigenetic Memory Underlies Cell-Autonomous Heterogeneous Behavior of Hematopoietic Stem Cells [J].

Yu, Vionnie W. C. ;

Yusuf, Rushdia Z. ;

Oki, Toshihiko ;

Wu, Juwell ;

Saez, Borja ;

Wang, Xin ;

Cook, Colleen ;

Baryawno, Ninib ;

Ziller, Michael J. ;

Lee, Eunjung ;

Gu, Hongcang ;

Meissner, Alexander ;

Lin, Charles P. ;

Kharchenko, Peter V. ;

Scadden, David T. .

CELL, 2016, 167 (05) :1310-+

← 1 2 3 →