Variation in hematopoietic potential of induced pluripotent stem cell lines.
Induced pluripotent stem (iPS) cells were originally generated from somatic cells by ectopic expression of four transcription factor genes: Oct3/4, Sox2, Klf4 and c-Myc. Currently, iPS cell lines differ in tissue origin, the combination of factors used to construct them, the method of gene delivery and expression of pluripotency markers. Thus to evaluate iPS cells for haematotherapy, the hematopoietic potential among iPS lines should be compared. Here, we compare differentiation capacity of six iPS lines into mesodermal cells and hematopoietic cells (HCs) through embryoid body (EB) formation. We show that the mouse embryonic fibroblast (MEF)-derived iPS lines 20D17 and 178B5 resemble CCE ES cells in terms of morphology in culture, number and size of EBs and differentiation capacity into mesodermal cells compared to iPS cells derived from adults, although all iPS lines could form EBs. The number of mesodermal cells differentiated from MEF-derived iPS cell lines showed a 3.9-407-fold increase compared to that from iPS lines derived from adults. Furthermore, 178B5 iPS cells generated Ter119(+) erythroid cells (3.35%) efficiently in culture. We conclude that hematopoietic potential differs among the six lines and that MEF-derived 20D17 and 178B5 iPS cells generate HCs more efficiently than adult-derived iPS cells.
Kulkeaw
Kasem
K
Department of Hematopoietic Stem Cells, SSP Stem Cell Unit, Faculty of Medical Sciences, Kyushu University, Station for Collaborative Research1 4F, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
Horio
Yuka
Y
Mizuochi
Chiyo
C
Ogawa
Minetaro
M
Sugiyama
Daisuke
D
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D058732:Embryoid Bodies / Q000166:cytology / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology*; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D000090062:Kruppel-Like Factor 4; D008648:Mesoderm / Q000502:physiology; D051379:Mice
Nature. 2007 Jul 19;448(7151):313-7
17554338
Cell. 2006 Aug 25;126(4):663-76
16904174
Curr Biol. 2008 Jun 24;18(12):890-4
18501604
Science. 1996 May 3;272(5262):722-4
8614833
Development. 1991 Feb;111(2):259-67
1893864
Science. 2008 Aug 1;321(5889):699-702
18276851
Blood. 2009 Dec 24;114(27):5473-80
19797525
Cell. 2008 Sep 5;134(5):877-86
18691744
Ann N Y Acad Sci. 2009 Sep;1176:219-27
19796250
Development. 2003 Sep;130(17):4217-27
12874139
Mol Cell Biol. 1993 Jan;13(1):473-86
8417345
Nat Biotechnol. 2009 Aug;27(8):743-5
19590502
Science. 2007 Dec 21;318(5858):1920-3
18063756
Nat Biotechnol. 2008 Jan;26(1):101-6
18059259
J Embryol Exp Morphol. 1985 Jun;87:27-45
3897439
BMC Biotechnol. 2002 Jun 11;2:11
12079497
Development. 1998 May;125(9):1747-57
9521912
Development. 1998 Feb;125(4):725-32
9435292
Science. 1994 Aug 19;265(5175):1098-101
8066449
Nature. 2004 Dec 2;432(7017):625-30
15577911
Dev Biol. 1995 Jun;169(2):699-712
7781909
Exp Hematol. 2010 Feb;38(2):154-62
19922768
Science. 2008 Nov 7;322(5903):949-53
18845712
Cell. 2008 Apr 18;133(2):250-64
18423197