Directed Differentiation of Escs and Ipscs Luis A

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SnapShot: Directed Differentiation of ESCs and iPSCs Luis A. Williams, Brandi N. Davis-Dusenbery, and Kevin C. Eggan HHMI, Harvard University, Cambridge, MA 02138, USA This SnapShot was previously published in Cell 149, May 25, 2012 ©2012 Elsevier Inc. DOI 10.1016/j.cell.2012.05.015

GERM C E LLS E C T O D E RM DE R I VAT IVES BMP4 BMP7 BMP8B Primordial germ Meiotic Haploid + + + transduction of cell-like cells cells cells DAZ genes Retinal pigment Epidermis epithelium Photoreceptors Otic hair cells Astrocytes Oligodendrocytes Cortical neurons Utricle Insulin RA FGF2H stroma SH oids Egf Taurine F GF n Culture on coculture T PD Reti + Neural crest hCG N p75+, HNK1 ACTIVIN A C Sort stem cells Spontaneous matrix Adherent Fgf2 culture FGF8 S Primordial germ differentiation Igf1 SHH e FGF2 r Oocyte-like Follicle-like u

cell-like cells EGF m cells + structures FGF SHH Ectoderm BMP4 Bmp4 Keratinocytes Neural Sort Scf GABA neurons DA neurons de NOGGIN progenitors R Transplantation Integrin- 3+ Lif Activin a A β DKK LDN/ SHH into testes Ssea1+ Egf Fgf2 Ascorbic Dorsomorphin WNT S acid tinami o o

c r i BMP4 t

Primordial germ Epiblast-like cells NODAL LEFTY Spinal motor neurons N Spermatozoa C

cell-like cells ACTIVIN D KSR or adherent culture

SB431542 3 Cortical layers + BMP4 PA6/MS-5 coculture Optic cup FGF2 Neural retina (NR ) EGF SFEBq culture 3D matrigel Retinal pigment VEGF Sort CXCR+,CD117 high ACTIVIN A Neuroectoderm culture epithelium (RPE )

Multipotent Deﬁnitive Pluripotent endodermal endoderm Stem Cells INSULIN, TRANSFERIN Serum Sort CD73+ FGF10 RA progenitor cells A-83-01 (ESCs/iPSCs) Selenium / Mesenchymal stem/ TGF OP-9 coculture FGF2, PDGF-BB OP-9 coculture precursor cells ACTIVIN BMP4 Semisolid NODAL β VEGF culture BMP4 Mesenchymo- Dexa, IBXT β-GP SCF angioblast Dexa HGF NOGGIN TPO FGF2 Insulin SB431542 Ascorbic Sort FGF4 FLT-3 ACTIVIN A Adipogenic cells EGF Hepatic WNT3A BMP4 Primitive streak acid NCAM+ FGF4 mesoderm progenitors Ascorbic acid VEGF, NT4 FGF10RA CSF, IL-3, IL-6 TGF 3 SCF, VEGF, BMP4 IL-3, IL-6, BMP4, FGF2 NT4, GDF5 β FOLLISTATIN BMP4, FGF2 Hepatocytes FLT-3, EPO, TPO IL-11, SCF SHH Osteogenic amine Semisolid BMP4 Chondrogenic cells N2 DAPT culture OP-9 -Serum Cyclop VEGF cells TPO coculture DKK DKK NOTCH Pancreatic progenitors EPO Anterior Hemangioblast Hematopoietic IL-3 WNT WNT progenitors IL-6 endoderm VEGF VEGF Skeletal IGF1 IL-11 myoblasts HGF EGF SCF Hindgut BMP4 SCF NOGGIN BMP4 Monocyte/ Cardiovascular Nicotinamide endoderm FGF2 TPO OP-9 or MS-5 macrophage WNTs colony-forming cells 3D matrigel IL-3 coculture progenitors culture FP6 EPO M-CSF Smooth β cells RANKL VEGF SB431542 FGF2 muscle cells

TGF β Multipotent Erythropoietic Lymphoid Intestinal lung progenitors cells progenitors Osteoclasts Fibronectin, EGM2 tissue Endothelial cells Cardiomyocytes END O DERM D ERIVAT I VES M E SODE R M DERIVAT I V E S

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