The Lin28b-let-7-Hmga2 axis determines the higher self-renewal potential of fetal haematopoietic stem cells

被引：276

作者：

Copley, Michael R. ^{[1
]}

Babovic, Sonja ^{[1
]}

Benz, Claudia ^{[1
]}

Knapp, David J. H. F. ^{[1
]}

Beer, Philip A. ^{[1
]}

Kent, David G. ^{[1
]}

Wohrer, Stefan ^{[1
]}

Treloar, David Q. ^{[1
]}

Day, Christopher ^{[1
]}

Rowe, Keegan ^{[1
]}

Mader, Heidi ^{[1
]}

Kuchenbauer, Florian ^{[1
]}

Humphries, R. Keith ^{[1
,2
,3
]}

Eaves, Connie J. ^{[1
,2
,3
]}

机构：

[1] BC Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada

[2] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada

[3] Univ British Columbia, Dept Med, Vancouver, BC V6T 1Z3, Canada

来源：

NATURE CELL BIOLOGY | 2013年 / 15卷 / 08期

基金：

加拿大健康研究院;

关键词：

PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; TRANSGENIC INSERTIONAL MUTANT; IN-VIVO; BONE-MARROW; LONG-TERM; CLONAL EXPANSION; MOLECULAR-BASIS; GENE-THERAPY; MINI-MOUSE; ADULT;

D O I：

10.1038/ncb2783

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Mouse haematopoietic stem cells (HSCs) undergo a postnatal transition in several properties, including a marked reduction in their self-renewal activity. We now show that the developmentally timed change in this key function of HSCs is associated with their decreased expression of Lin28b and an accompanying increase in their let-7 microRNA levels. Lentivirus-mediated overexpression of Lin28 in adult HSCs elevates their self-renewal activity in transplanted irradiated hosts, as does overexpression of Hmga2, a well-established let-7 target that is upregulated in fetal HSCs. Conversely, HSCs from fetal Hmga2(-/-) mice do not exhibit the heightened self-renewal activity that is characteristic of wild-type fetal HSCs. Interestingly, overexpression of Hmga2 in adult HSCs does not mimic the ability of elevated Lin28 to activate a fetal lymphoid differentiation program. Thus, Lin28b may act as a master regulator of developmentally timed changes in HSC programs with Hmga2 serving as its specific downstream modulator of HSC self-renewal potential.

引用

页码：916 / U341

页数：19

共 58 条

[1] MINI-MOUSE - PHENOTYPIC CHARACTERIZATION OF A TRANSGENIC INSERTIONAL MUTANT ALLELIC TO PYGMY [J].

BENSON, KF ;

CHADA, K .

GENETICAL RESEARCH, 1994, 64 (01) :27-33

[2] Hematopoietic Stem Cell Subtypes Expand Differentially during Development and Display Distinct Lymphopoietic Programs [J].

Benz, Claudia ;

Copley, Michael R. ;

Kent, David G. ;

Wohrer, Stefan ;

Cortes, Adrian ;

Aghaeepour, Nima ;

Ma, Elaine ;

Mader, Heidi ;

Rowe, Keegan ;

Day, Christopher ;

Treloar, David ;

Brinkman, Ryan R. ;

Eaves, Connie J. .

CELL STEM CELL, 2012, 10 (03) :273-283

[3] THE TOTAL MARROW MASS OF THE MOUSE - A SIMPLIFIED METHOD OF MEASUREMENT [J].

BOGGS, DR .

AMERICAN JOURNAL OF HEMATOLOGY, 1984, 16 (03) :277-286

[4] Identification of a new intrinsically timed developmental checkpoint that reprograms key hematopoietic stem cell properties [J].

Bowie, Michelle B. ;

Kent, David G. ;

Dykstra, Brad ;

McKnight, Kristen D. ;

McCaffrey, Lindsay ;

Hoodless, Pamela A. ;

Eaves, Connie J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (14) :5878-5882

[5] Hematopoietic stem cells proliferate until after birth and show a reversible phase-specific engraftment defect [J].

Bowie, Michelle B. ;

McKnight, Kristen D. ;

Kent, David G. ;

McCaffrey, Lindsay ;

Hoodless, Pamela A. ;

Eaves, Connie J. .

JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (10) :2808-2816

[6] Differential regulation of the insulin-like growth factor II mRNA-binding protein genes by architectural transcription factor HMGA2 [J].

Brants, JR ;

Ayoubi, TAY ;

Chada, K ;

Marchal, K ;

Van de Ven, WJM ;

Petit, MMR .

FEBS LETTERS, 2004, 569 (1-3) :277-283

[7] In vivo transduction by intravenous injection of a lentiviral vector expressing human ADA into neonatal ADA gene knockout mice:: A novel form of enzyme replacement therapy for ADA deficiency [J].

Carbonaro, Denise A. ;

Jin, Xiangyang ;

Petersen, Denise ;

Wang, Xingchao ;

Dorey, Fred ;

Kil, Ki Soo ;

Aldrich, Melissa ;

Blackburn, Michael R. ;

Kellems, Rodney E. ;

Kohn, Donald B. .

MOLECULAR THERAPY, 2006, 13 (06) :1110-1120

[8] Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia [J].

Cavazzana-Calvo, Marina ;

Payen, Emmanuel ;

Negre, Olivier ;

Wang, Gary ;

Hehir, Kathleen ;

Fusil, Floriane ;

Down, Julian ;

Denaro, Maria ;

Brady, Troy ;

Westerman, Karen ;

Cavallesco, Resy ;

Gillet-Legrand, Beatrix ;

Caccavelli, Laure ;

Sgarra, Riccardo ;

Maouche-Chretien, Leila ;

Bernaudin, Francoise ;

Girot, Robert ;

Dorazio, Ronald ;

Mulder, Geert-Jan ;

Polack, Axel ;

Bank, Arthur ;

Soulier, Jean ;

Larghero, Jerome ;

Kabbara, Nabil ;

Dalle, Bruno ;

Gourmel, Bernard ;

Socie, Gerard ;

Chretien, Stany ;

Cartier, Nathalie ;

Aubourg, Patrick ;

Fischer, Alain ;

Cornetta, Kenneth ;

Galacteros, Frederic ;

Beuzard, Yves ;

Gluckman, Eliane ;

Bushman, Frederick ;

Hacein-Bey-Abina, Salima ;

Leboulch, Philippe .

NATURE, 2010, 467 (7313) :318-U94

[9] MULTIPLE MODIFICATIONS IN CIS-ELEMENTS OF THE LONG TERMINAL REPEAT OF RETROVIRAL VECTORS LEAD TO INCREASED EXPRESSION AND DECREASED DNA METHYLATION IN EMBRYONIC CARCINOMA-CELLS [J].

CHALLITA, PM ;

SKELTON, D ;

ELKHOUEIRY, A ;

YU, XJ ;

WEINBERG, K ;

KOHN, DB .

JOURNAL OF VIROLOGY, 1995, 69 (02) :748-755

[10] HMGA2 regulates transcription of the Imp2 gene via an intronic regulatory element in cooperation with nuclear factor-κB [J].

Cleynen, Isabelle ;

Brants, Jan R. ;

Peeters, Kristel ;

Deckers, Rob ;

Debiec-Rychter, Maria ;

Sciot, Raf ;

de Ven, Wim J. M. Van ;

Petit, Marleen M. R. .

MOLECULAR CANCER RESEARCH, 2007, 5 (04) :363-372

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