Abstract
We have recently identified a stromal cell-derived inducing activity (SDIA), which induces differentiation of neural cells from mouse embryonic stem (ES) cells. Particularly, midbrain TH+dopaminergic neurons are generated efficiently in this system. These dopaminergic neurons are transplantable and survive well in the 6-OHDA-treated mouse striatum. SDIA induces co-cultured ES cells to differentiate into rostral central nervous system (CNS) tissues containing both ventral and dorsal cells. While early exposure of SDIA-treated ES cells to BMP4 suppresses neural differentiation and promotes epidermogenesis, late BMP4 exposure after the 4th day of co-culture causes differentiation of neural crest cells and dorsal-most CNS cells, with autonomic system and sensory lineages induced preferentially by high and low BMP4 concentrations, respectively. In contrast, Sonic Hedgehog (Shh) suppresses differentiation of neural crest lineages and promotes that of ventral CNS tissues such as motor neurons and HNF3ß + floor plate cells with axonal guidance activities. Thus, SDIA-treated ES cells generate naïve precursors that have the competence of differentiating into the “full” dorsal-ventral range of neuroectodermal derivatives in response to patterning signals. I also discuss the role of SDIA and the mode of rostral-caudal specification of neuralized ES cells. In addition, I would like to discuss them in the light of control of in vitro neural production for the use in regenerative medicine for parkinsonism and retinal degeneration.
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References
Bain G, Kitchens D, Yao M, Huettner JE, Gottlieb DI (1995). Embryonic stem cells express neuronal properties in vitro. Dev Biol 168:342–357
Haruta M, Sasai Y, Kawasaki H, Amemiya K, Ooto S, Kitada M, Suemori H, Nakatsuji N, Ide C, Honda Y, Takahashi M (2004) In vitro and in vivo characterization of pigment epithelial cells differentiated from primate embryonic stem cells. Invest Ophthalmol Vis Sci 45:1020–1025
Kawasaki H, Mizuseki K, Sasai Y (2001) Selective neural induction from ES cells by stromal cell-derived inducing activity and its possible application to parkinsonian therapy. In: Turksen K (ed) Methods in molecular biology. Humana Press, Totowa NJ, 217–228
Kawasaki H, Suemori H, Mizuseki K, Watanabe K, Urano F, Ichinose H, Haruta M, Takahashi M, Yoshikawa K, Nishikawa SI, Nakatsuji N, Sasai Y (2002) Generation of TH+ dopaminergic neurons, Pax6+ pigment epithelia from primate ES cells by SDIA. PNAS 99:1580–1585
Kawasaki H, Mizuseki K, Nishikawa S, Kaneko S, Kuwana Y, Nakanishi S, Nishikawa S-I, Sasai Y (2000) Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28:31–40
Kodama H, Hagiwara H, Sudo H, Amagai Y, Yokota T, Arai N, Kitamura Y (1986) MC3T3-G2/PA6 preadipocytes support in vitro proliferation of hemopoietic stem cells through a mechanism different from that of interleukin 3. J Cell Physiol 129:20–26
Lamb TM, Knecht AK, Smith WC, Stachel SE, Economides AN, Stahl N, Yancopolous GD, Harland RM (1993) Neural induction by the secreted polypeptide noggin. Science 262:713–718
Lee S-H, Lumelsky N, Studer L, Auerbach JM, McKay RD (2000). Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cell. Nature Biotech 18:675–679
Li LX, Turner JE (1988) Inherited retinal dystrophy in the RCS rat: prevention of photoreceptor degeneration by pigment epithelial cell transplantation. Exp Eye Res 47:911–917
Mizuseki K, Sakamoto T, Watanabe K, Muguruma K, Ikeya M, Nishiyama A, Arakawa A, Suemori H, Nakatsuji N, Kawasaki H, Murakami F, Sasai Y (2003) Generation of neural crest-derived PNS neurons, floor plate cells from mouse, primate ES Cells. Proc Natl Acad Sci U S A 100:5828–5833
Morizane A, Takahashi J, Takagi Y, Sasai Y, Hashimoto N (2002) Optimal conditions for in vivo induction of dopaminergic neurons from embryonic stem cells through stromal cell-derived inducing activity. J Neurosci Res 69934–69939
Ooto S, Haruta M, Honda Y, Kawasaki H, Sasai Y, Takahashi M(2003) Induction of the differentiation of lentoids from primate embryonic stem cells. Invest Ophthalmol Vis Sci 44:2689–2693
Sasai Y, De Robertis EM (1997) Ectodermal patterning in vertebrate embryos. Dev Biol 182:5–20
Sasai Y, Lu B, Steinbeisser H, De Robertis EM (1995) Regulation of neural induction by the chd, BMP-4 antagonistic patterning signals in Xenopus. Nature 376:333–336
Sasai Y (2000) Regulation of neural determination by evolutionally conserved signals: anti-BMP factors and what next? Curr Opin Neurobiol 11:22–26
Spemann H, Mangold H (1924) Über induktion von Embryonalagen durch Implantation Artfremder Organisatoren. Roux’ Arch Entw Mech 100:599–638
Suemori H, Tada T, Torii R et al. (2001) Establishment of embryonic stem cell lines from cynomolgus monkey blastocysts produced by IVF or ICSI. Dev Dyn. 222:273–279
Wilson PA, Hemmati-Brivanlou A (1995) Induction of epidermis and inhibition of neural fate by BMP-4. Nature 376:331–333
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Sasai, Y. (2005). Directed Differentiation of Neural and Sensory Tissues from Embryonic Stem Cells In Vitro. In: Morser, J., Nishikawa, S.I. (eds) The Promises and Challenges of Regenerative Medicine. Ernst Schering Research Foundation Workshop, vol 54. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-37644-5_7
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DOI: https://doi.org/10.1007/3-540-37644-5_7
Publisher Name: Springer, Berlin, Heidelberg
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