A critical role for Apc in hematopoietic stem and progenitor cell survival.

The Journal of Experimental Medicine
Zhijian QianMichelle M Le Beau

Abstract

The adenomatous polyposis coli (Apc) tumor suppressor is involved in the initiation and progression of colorectal cancer via regulation of the Wnt signaling cascade. In addition, Apc plays an important role in multiple cellular functions, including cell migration and adhesion, spindle assembly, and chromosome segregation. However, its role during adult hematopoiesis is unknown. We show that conditional inactivation of Apc in vivo dramatically increases apoptosis and enhances cell cycle entry of hematopoietic stem cells (HSCs)/ hematopoietic progenitor cells (HPCs), leading to their rapid disappearance and bone marrow failure. The defect in HSCs/HPCs caused by Apc ablation is cell autonomous. In addition, we found that loss of Apc leads to exhaustion of the myeloid progenitor pool (common myeloid progenitor, granulocyte-monocyte progenitor, and megakaryocyte-erythroid progenitor), as well as the lymphoid-primed multipotent progenitor pool. Down-regulation of the genes encoding Cdkn1a, Cdkn1b, and Mcl1 occurs after acute Apc excision in candidate HSC populations. Together, our data demonstrate that Apc is essential for HSC and HPC maintenance and survival.

References

Sep 8, 1995·Science·R KühnK Rajewsky
Apr 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K J SmithB Vogelstein
Apr 1, 1996·Hematology/oncology Clinics of North America·M J Thirman, R A Larson
Apr 1, 1997·The Journal of Pathology·C A MidgleyV J Bubb
Mar 10, 2000·Science·T ChengD T Scadden
Jan 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Sumitaka HasegawaTetsuo Noda
Mar 20, 2002·Nature Reviews. Cancer·R FoddeH Clevers
Apr 17, 2002·Cell·Jennifer AntonchukR Keith Humphries
Apr 30, 2003·Nature·Tannishtha ReyaIrving L Weissman
Sep 13, 2003·Science·Yukiko M YamashitaMargaret T Fuller
Oct 28, 2003·Nature Medicine·Jana KroslGuy Sauvageau
Jan 14, 2004·The Journal of Experimental Medicine·Monica CobasFreddy Radtke
Jun 17, 2004·Genes & Development·Owen J SansomDouglas J Winton
Sep 15, 2004·Current Opinion in Cell Biology·Mariann Bienz, Fumihiko Hamada
Nov 20, 2004·The Journal of Biological Chemistry·Chao-Nan QianBart O Williams
Feb 19, 2005·Science·Joseph T OpfermanStanley J Korsmeyer
Apr 2, 2005·The Journal of Biological Chemistry·Sheri L HolmenBart O Williams
Jul 19, 2005·Nature Immunology·Fotini GounariKhashayarsha Khazaie
Aug 24, 2005·Oncogene·Owen J SansomAlan R Clarke
Dec 13, 2005·Nature Medicine·Jennifer J TrowbridgeMickie Bhatia
Aug 22, 2006·Current Opinion in Genetics & Development·Omobolaji O Akala, Michael F Clarke
Oct 4, 2006·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Takeshi Kumagai
Dec 5, 2006·Oncogene·T Akiyama, Y Kawasaki
Apr 24, 2007·Cell·Jose M Galan-CaridadBoris Reizis

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Citations

Jan 9, 2009·Cell Stem Cell·Sachin Malhotra, Paul W Kincade
Mar 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Vitalyi SenyukZhijian Qian
Sep 26, 2013·The Journal of Experimental Medicine·Marie Le BouteillerMichel Cohen-Tannoudji
Jan 13, 2010·Blood·Jianghong WangZhijian Qian
Feb 15, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jordan LangFuzheng Guo
Jan 22, 2013·Biochimica Et Biophysica Acta·Maged Zeineldin, Kristi L Neufeld
Dec 5, 2009·Chemico-biological Interactions·Zhijian QianMichelle M Le Beau
Apr 7, 2009·Journal of Cellular Biochemistry·Bindya Jacob, Motomi Osato
May 26, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Jennifer R StevensTimothy F Lane
Jul 15, 2015·European Journal of Immunology·Jingjing CaoXizhi Guo
Nov 14, 2014·Journal of Thrombosis and Haemostasis : JTH·F PertuyC Léon
Apr 7, 2011·Leukemia Research·Joanna WegrzynAly Karsan
Oct 11, 2011·Cell Stem Cell·Tiago C LuisFrank J T Staal
Dec 3, 2009·Cell Stem Cell·Kamil R KrancTariq Enver
Nov 1, 2011·Blood·Michihiro Kobayashi, Edward F Srour
Jul 9, 2010·Blood·Anthony G PajerowskiVirginia Smith Shapiro
Aug 23, 2016·Leukemia & Lymphoma·Yi XiaoQiong Duan
Oct 12, 2018·Genes, Chromosomes & Cancer·Macoura Gadji, Aline Rangel Pozzo
Apr 13, 2013·Cancer Research·Maged Zeineldin, Kristi L Neufeld
Jan 17, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Florian H HeidelThomas Fischer
Nov 8, 2020·Molecular Cancer Therapeutics·Irum KhanAndrei L Gartel
Aug 22, 2020·Blood·Yue ShengZhijian Qian

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Methods Mentioned

BETA
nucleotide exchange
PCR
FACS
flow cytometry

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