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Generation of Dopamine Neurons from Rodent Fibroblasts through the Expandable Neural Precursor Cell Stage
Recent groundbreaking work has demonstrated that combined expression of the transcription factors Brn2, Ascl1, and Myt1L (BAM; also known as Wernig factors) convert mouse fibroblasts into postmitotic neuronal cells. However, questions remain regarding whether trans-conversion is achieved directly or...
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Published in: | The Journal of biological chemistry 2015-07, Vol.290 (28), p.17401-17414 |
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creator | Lim, Mi-Sun Chang, Mi-Yoon Kim, Sang-Mi Yi, Sang-Hoon Suh-Kim, Haeyoung Jung, Sung Jun Kim, Min Jung Kim, Jin Hyuk Lee, Yong-Sung Lee, Soo Young Kim, Dong-Wook Lee, Sang-Hun Park, Chang-Hwan |
description | Recent groundbreaking work has demonstrated that combined expression of the transcription factors Brn2, Ascl1, and Myt1L (BAM; also known as Wernig factors) convert mouse fibroblasts into postmitotic neuronal cells. However, questions remain regarding whether trans-conversion is achieved directly or involves an intermediary precursor stage. Trans-conversion toward expandable neural precursor cells (NPCs) is more useful than direct one-step neuron formation with respect to yielding a sufficient number of cells and the feasibility of manipulating NPC differentiation toward certain neuron subtypes. Here, we show that co-expression of Wernig factors and Bcl-xL induces fibroblast conversion into NPCs (induced NPCs (iNPCs)) that are highly expandable for >100 passages. Gene expression analyses showed that the iNPCs exhibited high expression of common NPC genes but not genes specific to defined embryonic brain regions. This finding indicated that a regional identity of iNPCs was not established. Upon induction, iNPCs predominantly differentiated into astrocytes. However, the differentiation potential was not fixed and could be efficiently manipulated into general or specific subtypes of neurons by expression of additional genes. Specifically, overexpression of Nurr1 and Foxa2, transcription factors specific for midbrain dopamine neuron development, drove iNPCs to yield mature midbrain dopamine neurons equipped with presynaptic DA neuronal functions. We further assessed the therapeutic potential of iNPCs in Parkinson disease model rats.
Background: Fibroblasts can be converted into neurons by transduction with BAM.
Results: Multiple lines of evidence were used to demonstrate that a significant percentage of BAM-transduced fibroblasts can be converted into iNPCs by co-expression of Bcl-xL.
Conclusion: BAMX-derived iNPCs were expandable over multiple passages in vitro, and differentiation phenotypes of iNPCs were readily manipulated by specific developmental cues.
Significance:Bcl-xL has a critical role in neural precursor cell conversion. |
doi_str_mv | 10.1074/jbc.M114.629808 |
format | article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4498077</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0021925820353448</els_id><sourcerecordid>1695756735</sourcerecordid><originalsourceid>FETCH-LOGICAL-c489t-5dd1ce4eaad688a8c5df3efbad16c810dc940668125b9f653ef75b01ee0699013</originalsourceid><addsrcrecordid>eNp1UU1P3DAQtapWZYGee6t85JLFTmLHvlSqlk8J2qqA1Jvl2JNdo8Re7ATBv69RAMGhc5nDvHnz5j2EvlKypKSpD29bs7yktF7yUgoiPqAFJaIqKkb_fkQLQkpayJKJHbSb0i3JVUv6Ge2UnJRVWVUL5E7BQ9SjCx6HDh-FrR6cB_wTphh8wl0MA_4TLPgRn7g2hrbXaUx43MQwrTe5Az5-2GpvddvPa7rHvyOYKaYQ8Qr6Hl-Neg376FOn-wRfnvseujk5vl6dFRe_Ts9XPy4KUws5FsxaaqAGrS0XQgvDbFdB12pLuRGUWCNrwrmgJWtlx1meNawlFIBwKQmt9tD3mXc7tQNYk5VnSWob3aDjowraqfcT7zZqHe5VXWcLmyYTHDwTxHA3QRrV4JLJf2gPYUqKcskaxpuKZejhDDUxpBShez1DiXoKSOWA1FNAag4ob3x7q-4V_5JIBsgZANmjewdRJePAG7AumzoqG9x_yf8BN46ibw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1695756735</pqid></control><display><type>article</type><title>Generation of Dopamine Neurons from Rodent Fibroblasts through the Expandable Neural Precursor Cell Stage</title><source>ScienceDirect</source><source>PubMed Central</source><creator>Lim, Mi-Sun ; Chang, Mi-Yoon ; Kim, Sang-Mi ; Yi, Sang-Hoon ; Suh-Kim, Haeyoung ; Jung, Sung Jun ; Kim, Min Jung ; Kim, Jin Hyuk ; Lee, Yong-Sung ; Lee, Soo Young ; Kim, Dong-Wook ; Lee, Sang-Hun ; Park, Chang-Hwan</creator><creatorcontrib>Lim, Mi-Sun ; Chang, Mi-Yoon ; Kim, Sang-Mi ; Yi, Sang-Hoon ; Suh-Kim, Haeyoung ; Jung, Sung Jun ; Kim, Min Jung ; Kim, Jin Hyuk ; Lee, Yong-Sung ; Lee, Soo Young ; Kim, Dong-Wook ; Lee, Sang-Hun ; Park, Chang-Hwan</creatorcontrib><description>Recent groundbreaking work has demonstrated that combined expression of the transcription factors Brn2, Ascl1, and Myt1L (BAM; also known as Wernig factors) convert mouse fibroblasts into postmitotic neuronal cells. However, questions remain regarding whether trans-conversion is achieved directly or involves an intermediary precursor stage. Trans-conversion toward expandable neural precursor cells (NPCs) is more useful than direct one-step neuron formation with respect to yielding a sufficient number of cells and the feasibility of manipulating NPC differentiation toward certain neuron subtypes. Here, we show that co-expression of Wernig factors and Bcl-xL induces fibroblast conversion into NPCs (induced NPCs (iNPCs)) that are highly expandable for >100 passages. Gene expression analyses showed that the iNPCs exhibited high expression of common NPC genes but not genes specific to defined embryonic brain regions. This finding indicated that a regional identity of iNPCs was not established. Upon induction, iNPCs predominantly differentiated into astrocytes. However, the differentiation potential was not fixed and could be efficiently manipulated into general or specific subtypes of neurons by expression of additional genes. Specifically, overexpression of Nurr1 and Foxa2, transcription factors specific for midbrain dopamine neuron development, drove iNPCs to yield mature midbrain dopamine neurons equipped with presynaptic DA neuronal functions. We further assessed the therapeutic potential of iNPCs in Parkinson disease model rats.
Background: Fibroblasts can be converted into neurons by transduction with BAM.
Results: Multiple lines of evidence were used to demonstrate that a significant percentage of BAM-transduced fibroblasts can be converted into iNPCs by co-expression of Bcl-xL.
Conclusion: BAMX-derived iNPCs were expandable over multiple passages in vitro, and differentiation phenotypes of iNPCs were readily manipulated by specific developmental cues.
Significance:Bcl-xL has a critical role in neural precursor cell conversion.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M114.629808</identifier><identifier>PMID: 26023233</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Basic Helix-Loop-Helix Transcription Factors - genetics ; cell therapy ; Cell Transdifferentiation ; Cellular Reprogramming ; Developmental Biology ; Dopamine - metabolism ; Dopaminergic Neurons - cytology ; Dopaminergic Neurons - metabolism ; Fibroblasts - cytology ; Fibroblasts - metabolism ; Gene Expression ; Hepatocyte Nuclear Factor 3-beta - genetics ; Mesencephalon - cytology ; Mesencephalon - metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Mice, Transgenic ; Nerve Tissue Proteins - genetics ; neural stem cell (NSC) ; Neural Stem Cells - cytology ; Neural Stem Cells - metabolism ; neurodegeneration ; Nuclear Receptor Subfamily 4, Group A, Member 2 - genetics ; Parkinson disease ; Parkinsonian Disorders - metabolism ; Parkinsonian Disorders - pathology ; Parkinsonian Disorders - therapy ; POU Domain Factors - genetics ; Rats ; Rats, Inbred Lew ; Rats, Wistar ; reprogramming ; Transcription Factors - genetics</subject><ispartof>The Journal of biological chemistry, 2015-07, Vol.290 (28), p.17401-17414</ispartof><rights>2015 © 2015 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2015 by The American Society for Biochemistry and Molecular Biology, Inc.</rights><rights>2015 by The American Society for Biochemistry and Molecular Biology, Inc. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c489t-5dd1ce4eaad688a8c5df3efbad16c810dc940668125b9f653ef75b01ee0699013</citedby><cites>FETCH-LOGICAL-c489t-5dd1ce4eaad688a8c5df3efbad16c810dc940668125b9f653ef75b01ee0699013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498077/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0021925820353448$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,3549,27924,27925,45780,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26023233$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lim, Mi-Sun</creatorcontrib><creatorcontrib>Chang, Mi-Yoon</creatorcontrib><creatorcontrib>Kim, Sang-Mi</creatorcontrib><creatorcontrib>Yi, Sang-Hoon</creatorcontrib><creatorcontrib>Suh-Kim, Haeyoung</creatorcontrib><creatorcontrib>Jung, Sung Jun</creatorcontrib><creatorcontrib>Kim, Min Jung</creatorcontrib><creatorcontrib>Kim, Jin Hyuk</creatorcontrib><creatorcontrib>Lee, Yong-Sung</creatorcontrib><creatorcontrib>Lee, Soo Young</creatorcontrib><creatorcontrib>Kim, Dong-Wook</creatorcontrib><creatorcontrib>Lee, Sang-Hun</creatorcontrib><creatorcontrib>Park, Chang-Hwan</creatorcontrib><title>Generation of Dopamine Neurons from Rodent Fibroblasts through the Expandable Neural Precursor Cell Stage</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Recent groundbreaking work has demonstrated that combined expression of the transcription factors Brn2, Ascl1, and Myt1L (BAM; also known as Wernig factors) convert mouse fibroblasts into postmitotic neuronal cells. However, questions remain regarding whether trans-conversion is achieved directly or involves an intermediary precursor stage. Trans-conversion toward expandable neural precursor cells (NPCs) is more useful than direct one-step neuron formation with respect to yielding a sufficient number of cells and the feasibility of manipulating NPC differentiation toward certain neuron subtypes. Here, we show that co-expression of Wernig factors and Bcl-xL induces fibroblast conversion into NPCs (induced NPCs (iNPCs)) that are highly expandable for >100 passages. Gene expression analyses showed that the iNPCs exhibited high expression of common NPC genes but not genes specific to defined embryonic brain regions. This finding indicated that a regional identity of iNPCs was not established. Upon induction, iNPCs predominantly differentiated into astrocytes. However, the differentiation potential was not fixed and could be efficiently manipulated into general or specific subtypes of neurons by expression of additional genes. Specifically, overexpression of Nurr1 and Foxa2, transcription factors specific for midbrain dopamine neuron development, drove iNPCs to yield mature midbrain dopamine neurons equipped with presynaptic DA neuronal functions. We further assessed the therapeutic potential of iNPCs in Parkinson disease model rats.
Background: Fibroblasts can be converted into neurons by transduction with BAM.
Results: Multiple lines of evidence were used to demonstrate that a significant percentage of BAM-transduced fibroblasts can be converted into iNPCs by co-expression of Bcl-xL.
Conclusion: BAMX-derived iNPCs were expandable over multiple passages in vitro, and differentiation phenotypes of iNPCs were readily manipulated by specific developmental cues.
Significance:Bcl-xL has a critical role in neural precursor cell conversion.</description><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>cell therapy</subject><subject>Cell Transdifferentiation</subject><subject>Cellular Reprogramming</subject><subject>Developmental Biology</subject><subject>Dopamine - metabolism</subject><subject>Dopaminergic Neurons - cytology</subject><subject>Dopaminergic Neurons - metabolism</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Gene Expression</subject><subject>Hepatocyte Nuclear Factor 3-beta - genetics</subject><subject>Mesencephalon - cytology</subject><subject>Mesencephalon - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred ICR</subject><subject>Mice, Transgenic</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>neural stem cell (NSC)</subject><subject>Neural Stem Cells - cytology</subject><subject>Neural Stem Cells - metabolism</subject><subject>neurodegeneration</subject><subject>Nuclear Receptor Subfamily 4, Group A, Member 2 - genetics</subject><subject>Parkinson disease</subject><subject>Parkinsonian Disorders - metabolism</subject><subject>Parkinsonian Disorders - pathology</subject><subject>Parkinsonian Disorders - therapy</subject><subject>POU Domain Factors - genetics</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>Rats, Wistar</subject><subject>reprogramming</subject><subject>Transcription Factors - genetics</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp1UU1P3DAQtapWZYGee6t85JLFTmLHvlSqlk8J2qqA1Jvl2JNdo8Re7ATBv69RAMGhc5nDvHnz5j2EvlKypKSpD29bs7yktF7yUgoiPqAFJaIqKkb_fkQLQkpayJKJHbSb0i3JVUv6Ge2UnJRVWVUL5E7BQ9SjCx6HDh-FrR6cB_wTphh8wl0MA_4TLPgRn7g2hrbXaUx43MQwrTe5Az5-2GpvddvPa7rHvyOYKaYQ8Qr6Hl-Neg376FOn-wRfnvseujk5vl6dFRe_Ts9XPy4KUws5FsxaaqAGrS0XQgvDbFdB12pLuRGUWCNrwrmgJWtlx1meNawlFIBwKQmt9tD3mXc7tQNYk5VnSWob3aDjowraqfcT7zZqHe5VXWcLmyYTHDwTxHA3QRrV4JLJf2gPYUqKcskaxpuKZejhDDUxpBShez1DiXoKSOWA1FNAag4ob3x7q-4V_5JIBsgZANmjewdRJePAG7AumzoqG9x_yf8BN46ibw</recordid><startdate>20150710</startdate><enddate>20150710</enddate><creator>Lim, Mi-Sun</creator><creator>Chang, Mi-Yoon</creator><creator>Kim, Sang-Mi</creator><creator>Yi, Sang-Hoon</creator><creator>Suh-Kim, Haeyoung</creator><creator>Jung, Sung Jun</creator><creator>Kim, Min Jung</creator><creator>Kim, Jin Hyuk</creator><creator>Lee, Yong-Sung</creator><creator>Lee, Soo Young</creator><creator>Kim, Dong-Wook</creator><creator>Lee, Sang-Hun</creator><creator>Park, Chang-Hwan</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150710</creationdate><title>Generation of Dopamine Neurons from Rodent Fibroblasts through the Expandable Neural Precursor Cell Stage</title><author>Lim, Mi-Sun ; Chang, Mi-Yoon ; Kim, Sang-Mi ; Yi, Sang-Hoon ; Suh-Kim, Haeyoung ; Jung, Sung Jun ; Kim, Min Jung ; Kim, Jin Hyuk ; Lee, Yong-Sung ; Lee, Soo Young ; Kim, Dong-Wook ; Lee, Sang-Hun ; Park, Chang-Hwan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c489t-5dd1ce4eaad688a8c5df3efbad16c810dc940668125b9f653ef75b01ee0699013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>cell therapy</topic><topic>Cell Transdifferentiation</topic><topic>Cellular Reprogramming</topic><topic>Developmental Biology</topic><topic>Dopamine - metabolism</topic><topic>Dopaminergic Neurons - cytology</topic><topic>Dopaminergic Neurons - metabolism</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - metabolism</topic><topic>Gene Expression</topic><topic>Hepatocyte Nuclear Factor 3-beta - genetics</topic><topic>Mesencephalon - cytology</topic><topic>Mesencephalon - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred ICR</topic><topic>Mice, Transgenic</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>neural stem cell (NSC)</topic><topic>Neural Stem Cells - cytology</topic><topic>Neural Stem Cells - metabolism</topic><topic>neurodegeneration</topic><topic>Nuclear Receptor Subfamily 4, Group A, Member 2 - genetics</topic><topic>Parkinson disease</topic><topic>Parkinsonian Disorders - metabolism</topic><topic>Parkinsonian Disorders - pathology</topic><topic>Parkinsonian Disorders - therapy</topic><topic>POU Domain Factors - genetics</topic><topic>Rats</topic><topic>Rats, Inbred Lew</topic><topic>Rats, Wistar</topic><topic>reprogramming</topic><topic>Transcription Factors - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lim, Mi-Sun</creatorcontrib><creatorcontrib>Chang, Mi-Yoon</creatorcontrib><creatorcontrib>Kim, Sang-Mi</creatorcontrib><creatorcontrib>Yi, Sang-Hoon</creatorcontrib><creatorcontrib>Suh-Kim, Haeyoung</creatorcontrib><creatorcontrib>Jung, Sung Jun</creatorcontrib><creatorcontrib>Kim, Min Jung</creatorcontrib><creatorcontrib>Kim, Jin Hyuk</creatorcontrib><creatorcontrib>Lee, Yong-Sung</creatorcontrib><creatorcontrib>Lee, Soo Young</creatorcontrib><creatorcontrib>Kim, Dong-Wook</creatorcontrib><creatorcontrib>Lee, Sang-Hun</creatorcontrib><creatorcontrib>Park, Chang-Hwan</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lim, Mi-Sun</au><au>Chang, Mi-Yoon</au><au>Kim, Sang-Mi</au><au>Yi, Sang-Hoon</au><au>Suh-Kim, Haeyoung</au><au>Jung, Sung Jun</au><au>Kim, Min Jung</au><au>Kim, Jin Hyuk</au><au>Lee, Yong-Sung</au><au>Lee, Soo Young</au><au>Kim, Dong-Wook</au><au>Lee, Sang-Hun</au><au>Park, Chang-Hwan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Generation of Dopamine Neurons from Rodent Fibroblasts through the Expandable Neural Precursor Cell Stage</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2015-07-10</date><risdate>2015</risdate><volume>290</volume><issue>28</issue><spage>17401</spage><epage>17414</epage><pages>17401-17414</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Recent groundbreaking work has demonstrated that combined expression of the transcription factors Brn2, Ascl1, and Myt1L (BAM; also known as Wernig factors) convert mouse fibroblasts into postmitotic neuronal cells. However, questions remain regarding whether trans-conversion is achieved directly or involves an intermediary precursor stage. Trans-conversion toward expandable neural precursor cells (NPCs) is more useful than direct one-step neuron formation with respect to yielding a sufficient number of cells and the feasibility of manipulating NPC differentiation toward certain neuron subtypes. Here, we show that co-expression of Wernig factors and Bcl-xL induces fibroblast conversion into NPCs (induced NPCs (iNPCs)) that are highly expandable for >100 passages. Gene expression analyses showed that the iNPCs exhibited high expression of common NPC genes but not genes specific to defined embryonic brain regions. This finding indicated that a regional identity of iNPCs was not established. Upon induction, iNPCs predominantly differentiated into astrocytes. However, the differentiation potential was not fixed and could be efficiently manipulated into general or specific subtypes of neurons by expression of additional genes. Specifically, overexpression of Nurr1 and Foxa2, transcription factors specific for midbrain dopamine neuron development, drove iNPCs to yield mature midbrain dopamine neurons equipped with presynaptic DA neuronal functions. We further assessed the therapeutic potential of iNPCs in Parkinson disease model rats.
Background: Fibroblasts can be converted into neurons by transduction with BAM.
Results: Multiple lines of evidence were used to demonstrate that a significant percentage of BAM-transduced fibroblasts can be converted into iNPCs by co-expression of Bcl-xL.
Conclusion: BAMX-derived iNPCs were expandable over multiple passages in vitro, and differentiation phenotypes of iNPCs were readily manipulated by specific developmental cues.
Significance:Bcl-xL has a critical role in neural precursor cell conversion.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26023233</pmid><doi>10.1074/jbc.M114.629808</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Basic Helix-Loop-Helix Transcription Factors - genetics cell therapy Cell Transdifferentiation Cellular Reprogramming Developmental Biology Dopamine - metabolism Dopaminergic Neurons - cytology Dopaminergic Neurons - metabolism Fibroblasts - cytology Fibroblasts - metabolism Gene Expression Hepatocyte Nuclear Factor 3-beta - genetics Mesencephalon - cytology Mesencephalon - metabolism Mice Mice, Inbred C57BL Mice, Inbred ICR Mice, Transgenic Nerve Tissue Proteins - genetics neural stem cell (NSC) Neural Stem Cells - cytology Neural Stem Cells - metabolism neurodegeneration Nuclear Receptor Subfamily 4, Group A, Member 2 - genetics Parkinson disease Parkinsonian Disorders - metabolism Parkinsonian Disorders - pathology Parkinsonian Disorders - therapy POU Domain Factors - genetics Rats Rats, Inbred Lew Rats, Wistar reprogramming Transcription Factors - genetics |
title | Generation of Dopamine Neurons from Rodent Fibroblasts through the Expandable Neural Precursor Cell Stage |
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