title: Sparse feature selection identifies H2A.Z as a novel, pattern-specific biomarker for asymmetrically self-renewing distributed stem cells.
abstract: There is a long-standing unmet clinical need for biomarkers with high specificity for distributed stem cells (DSCs) in tissues, or for use in diagnostic and therapeutic cell preparations (e.g., bone marrow). Although DSCs are essential for tissue maintenance and repair, accurate determination of their numbers for medical applications has been problematic. Previous searches for biomarkers expressed specifically in DSCs were hampered by difficulty obtaining pure DSCs and by the challenges in mining complex molecular expression data. To identify such useful and specific DSC biomarkers, we combined a novel sparse feature selection method with combinatorial molecular expression data focused on asymmetric self-renewal, a conspicuous property of DSCs. The analysis identified reduced expression of the histone H2A variant H2A.Z as a superior molecular discriminator for DSC asymmetric self-renewal. Subsequent molecular expression studies showed H2A.Z to be a novel "pattern-specific biomarker" for asymmetrically self-renewing cells, with sufficient specificity to count asymmetrically self-renewing DSCs in vitro and potentially in situ.
authors: Division of Electron Microscopic Research, Korea Basic Science Institute, 169-148 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors: Yang Hoon
authors: YH
authors: Huh
authors: College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors: Minsoo
authors: M
authors: Noh
authors: CSIRO Manufacturing Flagship, Clayton, Australia.
authors: Frank R
authors: FR
authors: Burden
authors: The Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Massachusetts Medical School, Worcester, MA, USA.
authors: Jennifer C
authors: JC
authors: Chen
authors: CSIRO Manufacturing Flagship, Clayton, Australia; Monash Institute of Pharmaceutical Sciences, Parkville, Australia; La Trobe Institute for Molecular Science, Bundoora, Australia. Electronic address: dave.winkler@csiro.au.
authors: David A
authors: DA
authors: Winkler
authors: Asymmetrex, LLC Boston, MA, USA. Electronic address: jlsherley@gmail.com.
authors: James L
authors: JL
authors: Sherley
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D046228:Microarray Analysis; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D006657:Histones
references: Mol Biol Cell. 1998 Jan;9(1):15-28
references: 9436988
references: Cancer Res. 2005 Apr 15;65(8):3155-61
references: 15833845
references: Stem Cells. 2012 Apr;30(4):591-8
references: 22331764
references: Science. 2002 Oct 18;298(5593):597-600
references: 12228720
references: Methods Mol Biol. 2010;673:283-95
references: 20835806
references: Nature. 1975 May 15;255(5505):197-200
references: 1143315
references: Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9127-32
references: 10922068
references: Cancer Res. 2002 Dec 1;62(23):6791-5
references: 12460886
references: Nat Genet. 2001 May;28(1):17-8
references: 11326268
references: Sci Rep. 2011;1:176
references: 22355691
references: Bioinformatics. 2006 Oct 1;22(19):2348-55
references: 16844704
references: Science. 2002 Oct 18;298(5593):601-4
references: 12228721
references: Cell Prolif. 1995 Mar;28(3):137-44
references: 7734623
references: Nat Rev Genet. 2001 Jun;2(6):418-27
references: 11389458
references: PLoS Biol. 2007 May;5(5):e102
references: 17439301
references: Blood. 1998 Jul 15;92(2):348-51; discussion 352
references: 9657728
references: J Cell Physiol. 1998 Nov;177(2):364-76
references: 9766533
references: Stem Cells Dev. 2011 Oct;20(10):1649-58
references: 21294632
references: Science. 2003 Oct 17;302(5644):393; author reply 393
references: 14563990
references: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2195-200
references: 20080668
references: Science. 2010 Jan 29;327(5965):542-5
references: 20110496
references: Eur J Hum Genet. 2012 Apr;20(4):404-10
references: 22108603
references: Stem Cells. 2011 Oct;29(10):1620-7
references: 21905168
references: J Cell Biol. 1963 May;17:299-313
references: 13985244
references: Dev Cell. 2002 Nov;3(5):612-3
references: 12431368
references: Stem Cells. 2002;20(6):561-72
references: 12456964
references: IEEE Trans Pattern Anal Mach Intell. 2004 Sep;26(9):1105-11
references: 15742887
references: PLoS One. 2011;6(7):e22077
references: 21818293
references: Nat Genet. 2000 Mar;24(3):227-35
references: 10700174
references: Development. 2011 Aug;138(15):3103-11
references: 21750026
references: Breast Dis. 2008;29:37-46
references: 19029623
references: Nat Genet. 2008 Nov;40(11):1291-9
references: 18849992
references: BMC Bioinformatics. 2008;9:195
references: 18410693
references: Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):4280-5
references: 25831522
references: J Biomed Biotechnol. 2001;1(1):28-37
references: 12488624
references: Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):136-40
references: 7816803
references: Nat Cell Biol. 2006 Jul;8(7):677-87
references: 16799552