Prdm12 regulates inhibitory neuron differentiation in mouse embryonal carcinoma cells

Baba, Akira; Suwada, Takuya; Muta, Shigeru; Kuhara, Satoru; Tashiro, Kosuke

doi:10.1007/s10616-022-00519-1

JAACT Issue
Published: 02 February 2022

Prdm12 regulates inhibitory neuron differentiation in mouse embryonal carcinoma cells

Akira Baba¹,
Takuya Suwada¹,
Shigeru Muta¹,
Satoru Kuhara¹ &
Kosuke Tashiro ORCID: orcid.org/0000-0003-4980-2058¹

Cytotechnology volume 74, pages 329–339 (2022)Cite this article

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Abstract

The epigenetic regulatory system significant influences the fate determination of cells during developmental processes. Prdm12 is a transcriptional regulator that modulates gene expression epigenetically. The Prdm12 gene has been shown to be expressed in neural tissues, specifically during development, but its detailed function is not fully understood. This study investigated the function of the Prdm12 gene in P19 mouse embryonic tumor cells as a model for neural differentiation. A decrease in the expression of neuron-specific genes and the alterations of dendrites and axons morphology was confirmed in Prdm12-knockout P19 cells. In addition, almost no astrocytes were generated in Prdm12-knockout P19 cells. Comprehensive gene expression analysis revealed that there was a reduction in the expression of the inhibitory neuron-specific genes Gad1/2 and Glyt2, but not the excitatory neuron-specific gene VGLUT2, in Prdm12-knockout P19 cells. Furthermore, the expression of inhibitory neuron-related factors, Ptf1a, Dbx1, and Gsx1/2, decreased in Prdm12-knockout P19 cells. Gene expression analysis also revealed that the Ptf1a, Hic1, and Foxa1 genes were candidate targets of Prdm12 during neurogenesis. These results suggest that Prdm12 regulates the differentiation of inhibitory neurons and astrocytes by controlling the expression of these genes during the neural differentiation of P19 cells.

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References

Achim K, Salminen M, Partanen J (2014) Mechanisms regulating GABAergic neuron development. Cell Mol Life Sci 71:1395–1415. https://doi.org/10.1007/s00018-013-1501-3
CAS Article PubMed Google Scholar
Bain G, Ray WJ, Yao M, Gottlieb DI (1994) From embryonal carcinoma cells to neurons: The P19 pathway. BioEssays 16:343–348
CAS Article Google Scholar
Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21:381–395. https://doi.org/10.1038/cr.2011.22
CAS Article PubMed PubMed Central Google Scholar
Barnabé-Heider F, Wasylnka JA, Fernandes KJL et al (2005) Evidence that embryonic neurons regulate the onset of cortical gliogenesis via cardiotrophin-1. Neuron 48:253–265. https://doi.org/10.1016/j.neuron.2005.08.037
CAS Article PubMed Google Scholar
Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21. https://doi.org/10.1101/gad.947102
CAS Article PubMed Google Scholar
Bovolenta P, Liem RKH, Mason CA (1984) Development of cerebellar astroglia: transitions in form and cytoskeletal content. Dev Biol 102:248–259. https://doi.org/10.1016/0012-1606(84)90189-1
CAS Article PubMed Google Scholar
Braat S, Kooy RF (2015) The GABAAReceptor as a therapeutic target for neurodevelopmental disorders. Neuron 86:1119–1130. https://doi.org/10.1016/j.neuron.2015.03.042
CAS Article PubMed Google Scholar
Chang JC, Meredith DM, Mayer PR et al (2013) Prdm13 mediates the balance of inhibitory and excitatory neurons in somatosensory circuits. Dev Cell 25:182–195. https://doi.org/10.1016/j.devcel.2013.02.015
CAS Article PubMed PubMed Central Google Scholar
Chen YC, Auer-Grumbach M, Matsukawa S et al (2015) Transcriptional regulator PRDM12 is essential for human pain perception. Nat Genet 47:803–808. https://doi.org/10.1038/ng.3308
CAS Article PubMed PubMed Central Google Scholar
Corbin JG, Rutlin M, Gaiano N, Fishell G (2003) Combinatorial function of the homeodomain proteins Nkx2.1 and Gsh2 in ventral telencephalic patterning. Development 130:4895–4906. https://doi.org/10.1242/dev.00717
CAS Article PubMed Google Scholar
Dahl D (1981) The vimentin-GFA protein transition in rat neuroglia cytoskeleton occurs at the time of myelination. J Neurosci Res 6:741–748. https://doi.org/10.1002/jnr.490060608
CAS Article PubMed Google Scholar
Desiderio S, Vermeiren S, Van Campenhout C et al (2019) Prdm12 directs nociceptive sensory neuron development by regulating the expression of the NGF receptor TrkA. Cell Rep 26:3522-3536.e5. https://doi.org/10.1016/j.celrep.2019.02.097
CAS Article PubMed Google Scholar
Eguchi R, Yoshigai E, Koga T et al (2015) Spatiotemporal expression of Prdm genes during Xenopus development. Cytotechnology 67:711–719. https://doi.org/10.1007/s10616-015-9846-0
CAS Article PubMed PubMed Central Google Scholar
Fardi M, Solali S, Farshdousti Hagh M (2018) Epigenetic mechanisms as a new approach in cancer treatment: an updated review. Genes Dis 5:304–311. https://doi.org/10.1016/j.gendis.2018.06.003
CAS Article PubMed PubMed Central Google Scholar
Feinberg AP (2007) Phenotypic plasticity and the epigenetics of human disease. Nature 447:433–440. https://doi.org/10.1038/nature05919
CAS Article PubMed Google Scholar
Fog CK, Galli GG, Lund AH (2012) PRDM proteins: important players in differentiation and disease. BioEssays 34:50–60. https://doi.org/10.1002/bies.201100107
CAS Article PubMed Google Scholar
Fujitani Y, Fujitani S, Luo H et al (2006) Ptf1a determines horizontal and amacrine cell fates during mouse retinal development. Development 133:4439–4450. https://doi.org/10.1242/dev.02598
CAS Article PubMed Google Scholar
Fremeau RT, Troyer MD, Pahner I et al (2001) The expression of vesicular glutamate transporters defines two classes of excitatory synapse. Neuron 31:247–260. https://doi.org/10.1016/S0896-6273(01)00344-0
CAS Article PubMed Google Scholar
Gelman D, Griveau A, Dehorter N et al (2011) A wide diversity of cortical GABAergic interneurons derives from the embryonic preoptic area. J Neurosci 31:16570–16580. https://doi.org/10.1523/JNEUROSCI.4068-11.2011
CAS Article PubMed PubMed Central Google Scholar
Gifford CA, Ziller MJ, Gu H et al (2013) Transcriptional and epigenetic dynamics during specification of human embryonic stem cells. Cell 153:1149–1163. https://doi.org/10.1016/j.cell.2013.04.037
CAS Article PubMed PubMed Central Google Scholar
Glasgow SM, Henke RM, MacDonald RJ et al (2005) Ptf1a determines GABAergic over glutamatergic neuronal cell fate in the spinal cord dorsal horn. Development 132:5461–5469. https://doi.org/10.1242/dev.02167
CAS Article PubMed Google Scholar
Hohenauer T, Moore AW (2012) The Prdm family: expanding roles in stem cells and development. Development 139:2267–2282. https://doi.org/10.1242/dev.070110
CAS Article PubMed Google Scholar
Hoshino M, Nakamura S, Mori K et al (2005) Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. Neuron 47:201–213. https://doi.org/10.1016/j.neuron.2005.06.007
CAS Article PubMed Google Scholar
Hu M, Sun XJ, Zhang YL et al (2010) Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling. Proc Natl Acad Sci USA 107:2956–2961. https://doi.org/10.1073/pnas.0915033107
Article PubMed PubMed Central Google Scholar
Jung CC, Atan D, Ng D et al (2015) Transcription factor PRDM8 is required for rod bipolar and type 2 OFF-cone bipolar cell survival and amacrine subtype identity. Proc Natl Acad Sci USA 112:E3010–E3019. https://doi.org/10.1073/pnas.1505870112
CAS Article PubMed PubMed Central Google Scholar
Kiehn O (2016) Decoding the organization of spinal circuits that control locomotion. Nat Rev Neurosci 17:224–238. https://doi.org/10.1038/nrn.2016.9
CAS Article PubMed PubMed Central Google Scholar
Kinameri E, Inoue T, Aruga J et al (2008) Prdm proto-oncogene transcription factor family expression and interaction with the Notch-Hes pathway in mouse neurogenesis. PLoS ONE 3:e3859. https://doi.org/10.1371/journal.pone.0003859
CAS Article PubMed PubMed Central Google Scholar
Komai T, Iwanari H, Mochizuki Y et al (2009) Expression of the mouse PR domain protein Prdm8 in the developing central nervous system. Gene Expr Patterns 9:503–514. https://doi.org/10.1016/j.gep.2009.07.005
CAS Article PubMed Google Scholar
Lanuza GM, Gosgnach S, Pierani A et al (2004) Genetic identification of spinal interneurons that coordinate left–right locomotor activity necessary for walking movements. Neuron 42:375–386. https://doi.org/10.1016/S0896-6273(04)00249-1
CAS Article PubMed Google Scholar
Lewis DA, Curley AA, Glausier JR, Volk DW (2012) Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia. Trends Neurosci 35:57–67. https://doi.org/10.1016/j.tins.2011.10.004
CAS Article PubMed Google Scholar
Martin DL, Rimvall K (1993) Regulation of y-aminobutyric acid synthesis in the brain. J Neurochem 60:395–407. https://doi.org/10.1111/j.1471-4159.1993.tb03165.x
CAS Article PubMed Google Scholar
McBurney MW, Reuhl KR, Ally AI et al (1988) Differentiation and maturation of embryonal carcinoma-derived neurons in cell culture. J Neurosci 8:1063–1073. https://doi.org/10.1523/jneurosci.08-03-01063.1988
CAS Article PubMed PubMed Central Google Scholar
McBurney MW, Rogers BJ (1982) Isolation of male embryonal carcinoma cells and their chromosome replication patterns. Dev Biol 89:503–508. https://doi.org/10.1016/0012-1606(82)90338-4
CAS Article PubMed Google Scholar
Mizuguchi R, Kriks S, Cordes R et al (2006) Ascl1 and Gsh1/2 control inhibitory and excitatory cell fate in spinal sensory interneurons. Nat Neurosci 9:770–778. https://doi.org/10.1038/nn1706
CAS Article PubMed Google Scholar
Mona B, Uruena A, Kollipara RK et al (2017) Repression by PRDM13 is critical for generating precision in neuronal identity. Elife 6:1–26. https://doi.org/10.7554/eLife.25787
Article Google Scholar
Ozeki H, Finn IM, Schaffer ES et al (2009) Inhibitory stabilization of the cortical network underlies visual surround suppression. Neuron 62:578–592. https://doi.org/10.1016/j.neuron.2009.03.028
CAS Article PubMed PubMed Central Google Scholar
Paridaen JT, Huttner WB (2014) Neurogenesis during development of the vertebrate central nervous system. EMBO Rep 15:351–364. https://doi.org/10.1002/embr.201438447
CAS Article PubMed PubMed Central Google Scholar
Pierani A, Moran-Rivard L, Sunshine MJ et al (2001) Control of interneuron fate in the developing spinal cord by the progenitor homeodomain protein Dbx1. Neuron 29:367–384. https://doi.org/10.1016/S0896-6273(01)00212-4
CAS Article PubMed Google Scholar
Ramamoorthi K, Lin Y (2011) The contribution of GABAergic dysfunction to neurodevelopmental disorders. Trends Mol Med 17:452–462. https://doi.org/10.1016/j.molmed.2011.03.003
CAS Article PubMed PubMed Central Google Scholar
Smith ZD, Meissner A (2013) DNA methylation: roles in mammalian development. Nat Rev Genet 14:204–220. https://doi.org/10.1038/nrg3354
CAS Article PubMed Google Scholar
Spike RC, Watt C, Zafra F, Todd AJ (1997) An ultrastructural study of the glycine transporter GLYT2 and its association with glycine in the superficial laminae of the rat spinal dorsal horn. Neuroscience 77:543–551. https://doi.org/10.1016/S0306-4522(96)00501-5
CAS Article PubMed Google Scholar
Thélie A, Desiderio S, Hanotel J et al (2015) Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus. Development 142:3416–3428
Article Google Scholar
Yagi M, Kabata M, Tanaka A et al (2020) Identification of distinct loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development. Nat Commun. https://doi.org/10.1038/s41467-020-16989-w
Article PubMed PubMed Central Google Scholar
Yang CM, Shinkai Y (2013) Prdm12 is induced by retinoic acid and exhibits anti-proliferative properties through the cell cycle modulation of P19 embryonic carcinoma cells. Cell Struct Funct 38:197–206. https://doi.org/10.1247/csf.13010
Article PubMed Google Scholar
Zafra F, Aragón C, Olivares L et al (1995) Glycine transporters are differentially expressed among CNS cells. J Neurosci 15:3952–3969. https://doi.org/10.1523/JNEUROSCI.15-05-03952.1995
CAS Article PubMed PubMed Central Google Scholar
Zhang Y, Xie S, Zhou Y et al (2014) H3K36 histone methyltransferase Setd2 is required for murine embryonic stem cell differentiation toward endoderm. Cell Rep 8:1989–2002. https://doi.org/10.1016/j.celrep.2014.08.031
CAS Article PubMed Google Scholar

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Acknowledgements

The authors would like to thank Dr. Shinobu Arai for her suggestions and Tomomi Kasa, Mamiko Ujihara, Hanaka Ono, and Akiko Enomoto for their advice.

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Authors and Affiliations

Molecular Gene Technics, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka-shi, Fukuoka, 8190395, Japan
Akira Baba, Takuya Suwada, Shigeru Muta, Satoru Kuhara & Kosuke Tashiro

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Akira Baba
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Takuya Suwada
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Shigeru Muta
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Satoru Kuhara
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Kosuke Tashiro
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Correspondence to Kosuke Tashiro.

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Baba, A., Suwada, T., Muta, S. et al. Prdm12 regulates inhibitory neuron differentiation in mouse embryonal carcinoma cells. Cytotechnology 74, 329–339 (2022). https://doi.org/10.1007/s10616-022-00519-1

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Received: 09 December 2021
Accepted: 04 January 2022
Published: 02 February 2022
Issue Date: April 2022
DOI: https://doi.org/10.1007/s10616-022-00519-1

Keywords

Prdm12
Neural. differentiation
Epigenetic
P19
Inhibitory neuron
Astrocyte