Tanycyte-Like Cells Derived From Mouse Embryonic Stem Culture Show Hypothalamic Neural Stem/Progenitor Cell Functions
Abstract Tanycytes have recently been accepted as neural stem/progenitor cells in the postnatal hypothalamus. Persistent retina and anterior neural fold homeobox (Rax) expression is characteristic of tanycytes in contrast to its transient expression of whole hypothalamic precursors. In this study, w...
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Veröffentlicht in: | Endocrinology (Philadelphia) 2019-07, Vol.160 (7), p.1701-1718 |
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creator | Kano, Mayuko Suga, Hidetaka Ishihara, Takeshi Sakakibara, Mayu Soen, Mika Yamada, Tomiko Ozaki, Hajime Mitsumoto, Kazuki Kasai, Takatoshi Sugiyama, Mariko Onoue, Takeshi Tsunekawa, Taku Takagi, Hiroshi Hagiwara, Daisuke Ito, Yoshihiro Iwama, Shintaro Goto, Motomitsu Banno, Ryoichi Arima, Hiroshi |
description | Abstract
Tanycytes have recently been accepted as neural stem/progenitor cells in the postnatal hypothalamus. Persistent retina and anterior neural fold homeobox (Rax) expression is characteristic of tanycytes in contrast to its transient expression of whole hypothalamic precursors. In this study, we found that Rax+ residual cells in the maturation phase of hypothalamic differentiation in mouse embryonic stem cell (mESC) cultures had similar characteristics to ventral tanycytes. They expressed typical neural stem/progenitor cell markers, including Sox2, vimentin, and nestin, and differentiated into mature neurons and glial cells. Quantitative RT-PCR analysis showed that Rax+ residual cells expressed Fgf-10, Fgf-18, and Lhx2, which are expressed by ventral tanycytes. They highly expressed tanycyte-specific genes Dio2 and Gpr50 compared with Rax+ early hypothalamic progenitor cells. Therefore, Rax+ residual cells in the maturation phase of hypothalamic differentiation were considered to be more differentiated and similar to late progenitor cells and tanycytes. They self-renewed and formed neurospheres when cultured with exogenous FGF-2. Additionally, these Rax+ neurospheres differentiated into three neuronal lineages (neurons, astrocytes, and oligodendrocytes), including neuropeptide Y+ neuron, that are reported to be differentiated from ventral tanycytes toward the arcuate nuclei. Thus, Rax+ residual cells were multipotent neural stem/progenitor cells. Rax+ neurospheres were stably passaged and retained high Sox2 expression even after multiple passages. These results suggest the successful induction of Rax+ tanycyte-like cells from mESCs [induced tanycyte-like (iTan) cells]. These hypothalamic neural stem/progenitor cells may have potential in regenerative medicine and as a research tool. |
doi_str_mv | 10.1210/en.2019-00105 |
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fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2232116428</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A615490710</galeid><oup_id>10.1210/en.2019-00105</oup_id><sourcerecordid>A615490710</sourcerecordid><originalsourceid>FETCH-LOGICAL-c504t-2ae003033ab36f42baa43c5bdc0fcf0fcce9d984a066701bcf392de6682ff6b63</originalsourceid><addsrcrecordid>eNp1kktv1DAUhS0EoqWwZIsssWGTqV9xJstq2qFIw0NqWVuOc92mJPbgByj_Hs9MoYBAlmXL_u7RuT5G6CUlC8ooOQW3YIS2FSGU1I_QMW1FXTW0IY9_2x-hZzHeFUQIwZ-iI04pr5ctPUb5WrvZzAmqzfAF8ArGMeJzCMM36PE6-Am_9zkCvpi6MHs3GHyVYMKrPKYcAF_d-u_4ct76dKtHPZXrD5CDHvfU6afgb8ANyYe9MF5nZ9LgXXyOnlg9Rnhxv56gz-uL69Vltfn49t3qbFOZmohUMQ2EcMK57ri0gnVaC27qrjfEGlumgbZvl0ITKRtCO2N5y3qQcsmslZ3kJ-jNQXcb_NcMMalpiKZY0Q5KW4oxziiVgi0L-vov9M7n4Io7xbisGW3qtn6gbvQIanDWp6DNTlSdSVqLljSUFGrxD6qMHsoTeQd2KOd_FFSHAhN8jAGs2oZh0mFWlKhdzAqc2sWs9jEX_tW92dxN0P-if-b60LjP2_9pHb4M_wEhpa2-</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2365217595</pqid></control><display><type>article</type><title>Tanycyte-Like Cells Derived From Mouse Embryonic Stem Culture Show Hypothalamic Neural Stem/Progenitor Cell Functions</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Kano, Mayuko ; Suga, Hidetaka ; Ishihara, Takeshi ; Sakakibara, Mayu ; Soen, Mika ; Yamada, Tomiko ; Ozaki, Hajime ; Mitsumoto, Kazuki ; Kasai, Takatoshi ; Sugiyama, Mariko ; Onoue, Takeshi ; Tsunekawa, Taku ; Takagi, Hiroshi ; Hagiwara, Daisuke ; Ito, Yoshihiro ; Iwama, Shintaro ; Goto, Motomitsu ; Banno, Ryoichi ; Arima, Hiroshi</creator><creatorcontrib>Kano, Mayuko ; Suga, Hidetaka ; Ishihara, Takeshi ; Sakakibara, Mayu ; Soen, Mika ; Yamada, Tomiko ; Ozaki, Hajime ; Mitsumoto, Kazuki ; Kasai, Takatoshi ; Sugiyama, Mariko ; Onoue, Takeshi ; Tsunekawa, Taku ; Takagi, Hiroshi ; Hagiwara, Daisuke ; Ito, Yoshihiro ; Iwama, Shintaro ; Goto, Motomitsu ; Banno, Ryoichi ; Arima, Hiroshi</creatorcontrib><description>Abstract
Tanycytes have recently been accepted as neural stem/progenitor cells in the postnatal hypothalamus. Persistent retina and anterior neural fold homeobox (Rax) expression is characteristic of tanycytes in contrast to its transient expression of whole hypothalamic precursors. In this study, we found that Rax+ residual cells in the maturation phase of hypothalamic differentiation in mouse embryonic stem cell (mESC) cultures had similar characteristics to ventral tanycytes. They expressed typical neural stem/progenitor cell markers, including Sox2, vimentin, and nestin, and differentiated into mature neurons and glial cells. Quantitative RT-PCR analysis showed that Rax+ residual cells expressed Fgf-10, Fgf-18, and Lhx2, which are expressed by ventral tanycytes. They highly expressed tanycyte-specific genes Dio2 and Gpr50 compared with Rax+ early hypothalamic progenitor cells. Therefore, Rax+ residual cells in the maturation phase of hypothalamic differentiation were considered to be more differentiated and similar to late progenitor cells and tanycytes. They self-renewed and formed neurospheres when cultured with exogenous FGF-2. Additionally, these Rax+ neurospheres differentiated into three neuronal lineages (neurons, astrocytes, and oligodendrocytes), including neuropeptide Y+ neuron, that are reported to be differentiated from ventral tanycytes toward the arcuate nuclei. Thus, Rax+ residual cells were multipotent neural stem/progenitor cells. Rax+ neurospheres were stably passaged and retained high Sox2 expression even after multiple passages. These results suggest the successful induction of Rax+ tanycyte-like cells from mESCs [induced tanycyte-like (iTan) cells]. These hypothalamic neural stem/progenitor cells may have potential in regenerative medicine and as a research tool.</description><identifier>ISSN: 1945-7170</identifier><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2019-00105</identifier><identifier>PMID: 31135891</identifier><language>eng</language><publisher>Washington, DC: Endocrine Society</publisher><subject>Animals ; Astrocytes ; Cell culture ; Cell differentiation ; Cell Lineage - physiology ; Cells, Cultured ; Differentiation ; Embryonic stem cells ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Endocrinology ; Ependymoglial Cells - cytology ; Ependymoglial Cells - metabolism ; Epithelial cells ; Fibroblast growth factor 10 ; Fibroblast Growth Factor 10 - metabolism ; Fibroblast growth factor 18 ; Fibroblast growth factor 2 ; Fibroblast Growth Factors - metabolism ; Glial cells ; Growth ; Homeobox ; Hypothalamus ; Hypothalamus (anterior) ; Hypothalamus - cytology ; Hypothalamus - metabolism ; LIM-Homeodomain Proteins - metabolism ; Maturation ; Methods ; Mice ; Nestin ; Neural stem cells ; Neural Stem Cells - cytology ; Neural Stem Cells - metabolism ; Neuronal-glial interactions ; Neurons ; Neuropeptide Y ; Neurospheres ; Nuclei (cytology) ; Oligodendrocytes ; Physiological aspects ; Polymerase chain reaction ; Progenitor cells ; Regenerative medicine ; Retina ; Stem cells ; Tanycytes ; Transcription Factors - metabolism ; Vimentin</subject><ispartof>Endocrinology (Philadelphia), 2019-07, Vol.160 (7), p.1701-1718</ispartof><rights>Copyright © 2019 Endocrine Society 2019</rights><rights>Copyright © 2019 Endocrine Society.</rights><rights>COPYRIGHT 2019 Oxford University Press</rights><rights>Copyright © 2019 Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-2ae003033ab36f42baa43c5bdc0fcf0fcce9d984a066701bcf392de6682ff6b63</citedby><cites>FETCH-LOGICAL-c504t-2ae003033ab36f42baa43c5bdc0fcf0fcce9d984a066701bcf392de6682ff6b63</cites><orcidid>0000-0002-2761-0461 ; 0000-0003-1924-7639</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31135891$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kano, Mayuko</creatorcontrib><creatorcontrib>Suga, Hidetaka</creatorcontrib><creatorcontrib>Ishihara, Takeshi</creatorcontrib><creatorcontrib>Sakakibara, Mayu</creatorcontrib><creatorcontrib>Soen, Mika</creatorcontrib><creatorcontrib>Yamada, Tomiko</creatorcontrib><creatorcontrib>Ozaki, Hajime</creatorcontrib><creatorcontrib>Mitsumoto, Kazuki</creatorcontrib><creatorcontrib>Kasai, Takatoshi</creatorcontrib><creatorcontrib>Sugiyama, Mariko</creatorcontrib><creatorcontrib>Onoue, Takeshi</creatorcontrib><creatorcontrib>Tsunekawa, Taku</creatorcontrib><creatorcontrib>Takagi, Hiroshi</creatorcontrib><creatorcontrib>Hagiwara, Daisuke</creatorcontrib><creatorcontrib>Ito, Yoshihiro</creatorcontrib><creatorcontrib>Iwama, Shintaro</creatorcontrib><creatorcontrib>Goto, Motomitsu</creatorcontrib><creatorcontrib>Banno, Ryoichi</creatorcontrib><creatorcontrib>Arima, Hiroshi</creatorcontrib><title>Tanycyte-Like Cells Derived From Mouse Embryonic Stem Culture Show Hypothalamic Neural Stem/Progenitor Cell Functions</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Abstract
Tanycytes have recently been accepted as neural stem/progenitor cells in the postnatal hypothalamus. Persistent retina and anterior neural fold homeobox (Rax) expression is characteristic of tanycytes in contrast to its transient expression of whole hypothalamic precursors. In this study, we found that Rax+ residual cells in the maturation phase of hypothalamic differentiation in mouse embryonic stem cell (mESC) cultures had similar characteristics to ventral tanycytes. They expressed typical neural stem/progenitor cell markers, including Sox2, vimentin, and nestin, and differentiated into mature neurons and glial cells. Quantitative RT-PCR analysis showed that Rax+ residual cells expressed Fgf-10, Fgf-18, and Lhx2, which are expressed by ventral tanycytes. They highly expressed tanycyte-specific genes Dio2 and Gpr50 compared with Rax+ early hypothalamic progenitor cells. Therefore, Rax+ residual cells in the maturation phase of hypothalamic differentiation were considered to be more differentiated and similar to late progenitor cells and tanycytes. They self-renewed and formed neurospheres when cultured with exogenous FGF-2. Additionally, these Rax+ neurospheres differentiated into three neuronal lineages (neurons, astrocytes, and oligodendrocytes), including neuropeptide Y+ neuron, that are reported to be differentiated from ventral tanycytes toward the arcuate nuclei. Thus, Rax+ residual cells were multipotent neural stem/progenitor cells. Rax+ neurospheres were stably passaged and retained high Sox2 expression even after multiple passages. These results suggest the successful induction of Rax+ tanycyte-like cells from mESCs [induced tanycyte-like (iTan) cells]. These hypothalamic neural stem/progenitor cells may have potential in regenerative medicine and as a research tool.</description><subject>Animals</subject><subject>Astrocytes</subject><subject>Cell culture</subject><subject>Cell differentiation</subject><subject>Cell Lineage - physiology</subject><subject>Cells, Cultured</subject><subject>Differentiation</subject><subject>Embryonic stem cells</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Endocrinology</subject><subject>Ependymoglial Cells - cytology</subject><subject>Ependymoglial Cells - metabolism</subject><subject>Epithelial cells</subject><subject>Fibroblast growth factor 10</subject><subject>Fibroblast Growth Factor 10 - metabolism</subject><subject>Fibroblast growth factor 18</subject><subject>Fibroblast growth factor 2</subject><subject>Fibroblast Growth Factors - metabolism</subject><subject>Glial cells</subject><subject>Growth</subject><subject>Homeobox</subject><subject>Hypothalamus</subject><subject>Hypothalamus (anterior)</subject><subject>Hypothalamus - cytology</subject><subject>Hypothalamus - metabolism</subject><subject>LIM-Homeodomain Proteins - metabolism</subject><subject>Maturation</subject><subject>Methods</subject><subject>Mice</subject><subject>Nestin</subject><subject>Neural stem cells</subject><subject>Neural Stem Cells - cytology</subject><subject>Neural Stem Cells - metabolism</subject><subject>Neuronal-glial interactions</subject><subject>Neurons</subject><subject>Neuropeptide Y</subject><subject>Neurospheres</subject><subject>Nuclei (cytology)</subject><subject>Oligodendrocytes</subject><subject>Physiological aspects</subject><subject>Polymerase chain reaction</subject><subject>Progenitor cells</subject><subject>Regenerative medicine</subject><subject>Retina</subject><subject>Stem cells</subject><subject>Tanycytes</subject><subject>Transcription Factors - metabolism</subject><subject>Vimentin</subject><issn>1945-7170</issn><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kktv1DAUhS0EoqWwZIsssWGTqV9xJstq2qFIw0NqWVuOc92mJPbgByj_Hs9MoYBAlmXL_u7RuT5G6CUlC8ooOQW3YIS2FSGU1I_QMW1FXTW0IY9_2x-hZzHeFUQIwZ-iI04pr5ctPUb5WrvZzAmqzfAF8ArGMeJzCMM36PE6-Am_9zkCvpi6MHs3GHyVYMKrPKYcAF_d-u_4ct76dKtHPZXrD5CDHvfU6afgb8ANyYe9MF5nZ9LgXXyOnlg9Rnhxv56gz-uL69Vltfn49t3qbFOZmohUMQ2EcMK57ri0gnVaC27qrjfEGlumgbZvl0ITKRtCO2N5y3qQcsmslZ3kJ-jNQXcb_NcMMalpiKZY0Q5KW4oxziiVgi0L-vov9M7n4Io7xbisGW3qtn6gbvQIanDWp6DNTlSdSVqLljSUFGrxD6qMHsoTeQd2KOd_FFSHAhN8jAGs2oZh0mFWlKhdzAqc2sWs9jEX_tW92dxN0P-if-b60LjP2_9pHb4M_wEhpa2-</recordid><startdate>20190701</startdate><enddate>20190701</enddate><creator>Kano, Mayuko</creator><creator>Suga, Hidetaka</creator><creator>Ishihara, Takeshi</creator><creator>Sakakibara, Mayu</creator><creator>Soen, Mika</creator><creator>Yamada, Tomiko</creator><creator>Ozaki, Hajime</creator><creator>Mitsumoto, Kazuki</creator><creator>Kasai, Takatoshi</creator><creator>Sugiyama, Mariko</creator><creator>Onoue, Takeshi</creator><creator>Tsunekawa, Taku</creator><creator>Takagi, Hiroshi</creator><creator>Hagiwara, Daisuke</creator><creator>Ito, Yoshihiro</creator><creator>Iwama, Shintaro</creator><creator>Goto, Motomitsu</creator><creator>Banno, Ryoichi</creator><creator>Arima, Hiroshi</creator><general>Endocrine Society</general><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2761-0461</orcidid><orcidid>https://orcid.org/0000-0003-1924-7639</orcidid></search><sort><creationdate>20190701</creationdate><title>Tanycyte-Like Cells Derived From Mouse Embryonic Stem Culture Show Hypothalamic Neural Stem/Progenitor Cell Functions</title><author>Kano, Mayuko ; Suga, Hidetaka ; Ishihara, Takeshi ; Sakakibara, Mayu ; Soen, Mika ; Yamada, Tomiko ; Ozaki, Hajime ; Mitsumoto, Kazuki ; Kasai, Takatoshi ; Sugiyama, Mariko ; Onoue, Takeshi ; Tsunekawa, Taku ; Takagi, Hiroshi ; Hagiwara, Daisuke ; Ito, Yoshihiro ; Iwama, Shintaro ; Goto, Motomitsu ; Banno, Ryoichi ; Arima, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-2ae003033ab36f42baa43c5bdc0fcf0fcce9d984a066701bcf392de6682ff6b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Astrocytes</topic><topic>Cell culture</topic><topic>Cell differentiation</topic><topic>Cell Lineage - physiology</topic><topic>Cells, Cultured</topic><topic>Differentiation</topic><topic>Embryonic stem cells</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Endocrinology</topic><topic>Ependymoglial Cells - cytology</topic><topic>Ependymoglial Cells - metabolism</topic><topic>Epithelial cells</topic><topic>Fibroblast growth factor 10</topic><topic>Fibroblast Growth Factor 10 - metabolism</topic><topic>Fibroblast growth factor 18</topic><topic>Fibroblast growth factor 2</topic><topic>Fibroblast Growth Factors - metabolism</topic><topic>Glial cells</topic><topic>Growth</topic><topic>Homeobox</topic><topic>Hypothalamus</topic><topic>Hypothalamus (anterior)</topic><topic>Hypothalamus - cytology</topic><topic>Hypothalamus - metabolism</topic><topic>LIM-Homeodomain Proteins - metabolism</topic><topic>Maturation</topic><topic>Methods</topic><topic>Mice</topic><topic>Nestin</topic><topic>Neural stem cells</topic><topic>Neural Stem Cells - cytology</topic><topic>Neural Stem Cells - metabolism</topic><topic>Neuronal-glial interactions</topic><topic>Neurons</topic><topic>Neuropeptide Y</topic><topic>Neurospheres</topic><topic>Nuclei (cytology)</topic><topic>Oligodendrocytes</topic><topic>Physiological aspects</topic><topic>Polymerase chain reaction</topic><topic>Progenitor cells</topic><topic>Regenerative medicine</topic><topic>Retina</topic><topic>Stem cells</topic><topic>Tanycytes</topic><topic>Transcription Factors - metabolism</topic><topic>Vimentin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kano, Mayuko</creatorcontrib><creatorcontrib>Suga, Hidetaka</creatorcontrib><creatorcontrib>Ishihara, Takeshi</creatorcontrib><creatorcontrib>Sakakibara, Mayu</creatorcontrib><creatorcontrib>Soen, Mika</creatorcontrib><creatorcontrib>Yamada, Tomiko</creatorcontrib><creatorcontrib>Ozaki, Hajime</creatorcontrib><creatorcontrib>Mitsumoto, Kazuki</creatorcontrib><creatorcontrib>Kasai, Takatoshi</creatorcontrib><creatorcontrib>Sugiyama, Mariko</creatorcontrib><creatorcontrib>Onoue, Takeshi</creatorcontrib><creatorcontrib>Tsunekawa, Taku</creatorcontrib><creatorcontrib>Takagi, Hiroshi</creatorcontrib><creatorcontrib>Hagiwara, Daisuke</creatorcontrib><creatorcontrib>Ito, Yoshihiro</creatorcontrib><creatorcontrib>Iwama, Shintaro</creatorcontrib><creatorcontrib>Goto, Motomitsu</creatorcontrib><creatorcontrib>Banno, Ryoichi</creatorcontrib><creatorcontrib>Arima, Hiroshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kano, Mayuko</au><au>Suga, Hidetaka</au><au>Ishihara, Takeshi</au><au>Sakakibara, Mayu</au><au>Soen, Mika</au><au>Yamada, Tomiko</au><au>Ozaki, Hajime</au><au>Mitsumoto, Kazuki</au><au>Kasai, Takatoshi</au><au>Sugiyama, Mariko</au><au>Onoue, Takeshi</au><au>Tsunekawa, Taku</au><au>Takagi, Hiroshi</au><au>Hagiwara, Daisuke</au><au>Ito, Yoshihiro</au><au>Iwama, Shintaro</au><au>Goto, Motomitsu</au><au>Banno, Ryoichi</au><au>Arima, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tanycyte-Like Cells Derived From Mouse Embryonic Stem Culture Show Hypothalamic Neural Stem/Progenitor Cell Functions</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2019-07-01</date><risdate>2019</risdate><volume>160</volume><issue>7</issue><spage>1701</spage><epage>1718</epage><pages>1701-1718</pages><issn>1945-7170</issn><issn>0013-7227</issn><eissn>1945-7170</eissn><abstract>Abstract
Tanycytes have recently been accepted as neural stem/progenitor cells in the postnatal hypothalamus. Persistent retina and anterior neural fold homeobox (Rax) expression is characteristic of tanycytes in contrast to its transient expression of whole hypothalamic precursors. In this study, we found that Rax+ residual cells in the maturation phase of hypothalamic differentiation in mouse embryonic stem cell (mESC) cultures had similar characteristics to ventral tanycytes. They expressed typical neural stem/progenitor cell markers, including Sox2, vimentin, and nestin, and differentiated into mature neurons and glial cells. Quantitative RT-PCR analysis showed that Rax+ residual cells expressed Fgf-10, Fgf-18, and Lhx2, which are expressed by ventral tanycytes. They highly expressed tanycyte-specific genes Dio2 and Gpr50 compared with Rax+ early hypothalamic progenitor cells. Therefore, Rax+ residual cells in the maturation phase of hypothalamic differentiation were considered to be more differentiated and similar to late progenitor cells and tanycytes. They self-renewed and formed neurospheres when cultured with exogenous FGF-2. Additionally, these Rax+ neurospheres differentiated into three neuronal lineages (neurons, astrocytes, and oligodendrocytes), including neuropeptide Y+ neuron, that are reported to be differentiated from ventral tanycytes toward the arcuate nuclei. Thus, Rax+ residual cells were multipotent neural stem/progenitor cells. Rax+ neurospheres were stably passaged and retained high Sox2 expression even after multiple passages. These results suggest the successful induction of Rax+ tanycyte-like cells from mESCs [induced tanycyte-like (iTan) cells]. These hypothalamic neural stem/progenitor cells may have potential in regenerative medicine and as a research tool.</abstract><cop>Washington, DC</cop><pub>Endocrine Society</pub><pmid>31135891</pmid><doi>10.1210/en.2019-00105</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-2761-0461</orcidid><orcidid>https://orcid.org/0000-0003-1924-7639</orcidid><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
subjects | Animals Astrocytes Cell culture Cell differentiation Cell Lineage - physiology Cells, Cultured Differentiation Embryonic stem cells Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Endocrinology Ependymoglial Cells - cytology Ependymoglial Cells - metabolism Epithelial cells Fibroblast growth factor 10 Fibroblast Growth Factor 10 - metabolism Fibroblast growth factor 18 Fibroblast growth factor 2 Fibroblast Growth Factors - metabolism Glial cells Growth Homeobox Hypothalamus Hypothalamus (anterior) Hypothalamus - cytology Hypothalamus - metabolism LIM-Homeodomain Proteins - metabolism Maturation Methods Mice Nestin Neural stem cells Neural Stem Cells - cytology Neural Stem Cells - metabolism Neuronal-glial interactions Neurons Neuropeptide Y Neurospheres Nuclei (cytology) Oligodendrocytes Physiological aspects Polymerase chain reaction Progenitor cells Regenerative medicine Retina Stem cells Tanycytes Transcription Factors - metabolism Vimentin |
title | Tanycyte-Like Cells Derived From Mouse Embryonic Stem Culture Show Hypothalamic Neural Stem/Progenitor Cell Functions |
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