Transcription factor-based transdifferentiation of human embryonic to trophoblast stem cells
During the first week of development, human embryos form a blastocyst composed of an inner cell mass and trophectoderm (TE) cells, the latter of which are progenitors of placental trophoblast. Here, we investigated the expression of transcripts in the human TE from early to late blastocyst stages. W...
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| Veröffentlicht in: | Development (Cambridge) 2024-09, Vol.151 (17) |
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| creator | Balestrini, Paula A Abdelbaki, Ahmed McCarthy, Afshan Devito, Liani Senner, Claire E Chen, Alice E Munusamy, Prabhakaran Blakeley, Paul Elder, Kay Snell, Phil Christie, Leila Serhal, Paul Odia, Rabi A Sangrithi, Mahesh Niakan, Kathy K Fogarty, Norah M E |
| description | During the first week of development, human embryos form a blastocyst composed of an inner cell mass and trophectoderm (TE) cells, the latter of which are progenitors of placental trophoblast. Here, we investigated the expression of transcripts in the human TE from early to late blastocyst stages. We identified enrichment of the transcription factors GATA2, GATA3, TFAP2C and KLF5 and characterised their protein expression dynamics across TE development. By inducible overexpression and mRNA transfection, we determined that these factors, together with MYC, are sufficient to establish induced trophoblast stem cells (iTSCs) from primed human embryonic stem cells. These iTSCs self-renew and recapitulate morphological characteristics, gene expression profiles, and directed differentiation potential, similar to existing human TSCs. Systematic omission of each, or combinations of factors, revealed the crucial importance of GATA2 and GATA3 for iTSC transdifferentiation. Altogether, these findings provide insights into the transcription factor network that may be operational in the human TE and broaden the methods for establishing cellular models of early human placental progenitor cells, which may be useful in the future to model placental-associated diseases. |
| doi_str_mv | 10.1242/dev.202778 |
| format | Article |
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Here, we investigated the expression of transcripts in the human TE from early to late blastocyst stages. We identified enrichment of the transcription factors GATA2, GATA3, TFAP2C and KLF5 and characterised their protein expression dynamics across TE development. By inducible overexpression and mRNA transfection, we determined that these factors, together with MYC, are sufficient to establish induced trophoblast stem cells (iTSCs) from primed human embryonic stem cells. These iTSCs self-renew and recapitulate morphological characteristics, gene expression profiles, and directed differentiation potential, similar to existing human TSCs. Systematic omission of each, or combinations of factors, revealed the crucial importance of GATA2 and GATA3 for iTSC transdifferentiation. Altogether, these findings provide insights into the transcription factor network that may be operational in the human TE and broaden the methods for establishing cellular models of early human placental progenitor cells, which may be useful in the future to model placental-associated diseases.</description><identifier>ISSN: 0950-1991</identifier><identifier>ISSN: 1477-9129</identifier><identifier>EISSN: 1477-9129</identifier><identifier>DOI: 10.1242/dev.202778</identifier><identifier>PMID: 39250534</identifier><language>eng</language><publisher>England: The Company of Biologists Ltd</publisher><subject>Blastocyst - cytology ; Blastocyst - metabolism ; Cell Differentiation ; Cell Transdifferentiation ; Female ; GATA2 Transcription Factor - genetics ; GATA2 Transcription Factor - metabolism ; GATA3 Transcription Factor - genetics ; GATA3 Transcription Factor - metabolism ; Gene Expression Regulation, Developmental ; Human Embryonic Stem Cells - cytology ; Human Embryonic Stem Cells - metabolism ; Humans ; Pregnancy ; Techniques and Resources ; Transcription Factor AP-2 - genetics ; Transcription Factor AP-2 - metabolism ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Trophoblasts - cytology ; Trophoblasts - metabolism</subject><ispartof>Development (Cambridge), 2024-09, Vol.151 (17)</ispartof><rights>2024. 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Published by The Company of Biologists Ltd 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c268t-77874ff5438de561727d4206d7914dd7162686e2a208d7120b8ae44338da011a3</cites><orcidid>0000-0003-1670-0311 ; 0000-0003-1085-8185 ; 0000-0003-1646-4734 ; 0000-0002-9351-1226 ; 0000-0001-5237-3165</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,3665,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39250534$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Balestrini, Paula A</creatorcontrib><creatorcontrib>Abdelbaki, Ahmed</creatorcontrib><creatorcontrib>McCarthy, Afshan</creatorcontrib><creatorcontrib>Devito, Liani</creatorcontrib><creatorcontrib>Senner, Claire E</creatorcontrib><creatorcontrib>Chen, Alice E</creatorcontrib><creatorcontrib>Munusamy, Prabhakaran</creatorcontrib><creatorcontrib>Blakeley, Paul</creatorcontrib><creatorcontrib>Elder, Kay</creatorcontrib><creatorcontrib>Snell, Phil</creatorcontrib><creatorcontrib>Christie, Leila</creatorcontrib><creatorcontrib>Serhal, Paul</creatorcontrib><creatorcontrib>Odia, Rabi A</creatorcontrib><creatorcontrib>Sangrithi, Mahesh</creatorcontrib><creatorcontrib>Niakan, Kathy K</creatorcontrib><creatorcontrib>Fogarty, Norah M E</creatorcontrib><title>Transcription factor-based transdifferentiation of human embryonic to trophoblast stem cells</title><title>Development (Cambridge)</title><addtitle>Development</addtitle><description>During the first week of development, human embryos form a blastocyst composed of an inner cell mass and trophectoderm (TE) cells, the latter of which are progenitors of placental trophoblast. 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Altogether, these findings provide insights into the transcription factor network that may be operational in the human TE and broaden the methods for establishing cellular models of early human placental progenitor cells, which may be useful in the future to model placental-associated diseases.</description><subject>Blastocyst - cytology</subject><subject>Blastocyst - metabolism</subject><subject>Cell Differentiation</subject><subject>Cell Transdifferentiation</subject><subject>Female</subject><subject>GATA2 Transcription Factor - genetics</subject><subject>GATA2 Transcription Factor - metabolism</subject><subject>GATA3 Transcription Factor - genetics</subject><subject>GATA3 Transcription Factor - metabolism</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Human Embryonic Stem Cells - cytology</subject><subject>Human Embryonic Stem Cells - metabolism</subject><subject>Humans</subject><subject>Pregnancy</subject><subject>Techniques and Resources</subject><subject>Transcription Factor AP-2 - genetics</subject><subject>Transcription Factor AP-2 - metabolism</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Trophoblasts - cytology</subject><subject>Trophoblasts - metabolism</subject><issn>0950-1991</issn><issn>1477-9129</issn><issn>1477-9129</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkV9LwzAUxYMobk5f_ADSRxE6c5O0aZ9Ehv9g4Mt8E0LapC7SNjNJB_v2Zm4Ofbpczo9zz-UgdAl4CoSRW6XXU4IJ58URGgPjPC2BlMdojMsMp1CWMEJn3n9ijGnO-Ska0ZJkOKNsjN4XTva-dmYVjO2TRtbBurSSXqskbCVlmkY73QcjfwjbJMuhk32iu8ptbG_qJNiI2tXSVq30IfFBd0mt29afo5NGtl5f7OcEvT0-LGbP6fz16WV2P09rkhchjcE5a5qM0ULpLAdOuGIE54qXwJTikEcs10QSXMSN4KqQmjEacYkBJJ2gu53vaqg6reqY1slWrJzppNsIK434r_RmKT7sWgBkWU6BRYfrvYOzX4P2QXTGb3-QvbaDFxQwYRwDxRG92aG1s9473RzuABbbPkTsQ-z6iPDV32QH9LcA-g0bW4fS</recordid><startdate>20240901</startdate><enddate>20240901</enddate><creator>Balestrini, Paula A</creator><creator>Abdelbaki, Ahmed</creator><creator>McCarthy, Afshan</creator><creator>Devito, Liani</creator><creator>Senner, Claire E</creator><creator>Chen, Alice E</creator><creator>Munusamy, Prabhakaran</creator><creator>Blakeley, Paul</creator><creator>Elder, Kay</creator><creator>Snell, Phil</creator><creator>Christie, Leila</creator><creator>Serhal, Paul</creator><creator>Odia, Rabi A</creator><creator>Sangrithi, Mahesh</creator><creator>Niakan, Kathy K</creator><creator>Fogarty, Norah M E</creator><general>The Company of Biologists Ltd</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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1670-0311</orcidid><orcidid>https://orcid.org/0000-0003-1085-8185</orcidid><orcidid>https://orcid.org/0000-0003-1646-4734</orcidid><orcidid>https://orcid.org/0000-0002-9351-1226</orcidid><orcidid>https://orcid.org/0000-0001-5237-3165</orcidid></search><sort><creationdate>20240901</creationdate><title>Transcription factor-based transdifferentiation of human embryonic to trophoblast stem cells</title><author>Balestrini, Paula A ; Abdelbaki, Ahmed ; McCarthy, Afshan ; Devito, Liani ; Senner, Claire E ; Chen, Alice E ; Munusamy, Prabhakaran ; Blakeley, Paul ; Elder, Kay ; Snell, Phil ; Christie, Leila ; Serhal, Paul ; Odia, Rabi A ; Sangrithi, Mahesh ; Niakan, Kathy K ; Fogarty, Norah M E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c268t-77874ff5438de561727d4206d7914dd7162686e2a208d7120b8ae44338da011a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Blastocyst - cytology</topic><topic>Blastocyst - metabolism</topic><topic>Cell Differentiation</topic><topic>Cell Transdifferentiation</topic><topic>Female</topic><topic>GATA2 Transcription Factor - genetics</topic><topic>GATA2 Transcription Factor - metabolism</topic><topic>GATA3 Transcription Factor - genetics</topic><topic>GATA3 Transcription Factor - metabolism</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Human Embryonic Stem Cells - cytology</topic><topic>Human Embryonic Stem Cells - metabolism</topic><topic>Humans</topic><topic>Pregnancy</topic><topic>Techniques and Resources</topic><topic>Transcription Factor AP-2 - genetics</topic><topic>Transcription Factor AP-2 - metabolism</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Trophoblasts - cytology</topic><topic>Trophoblasts - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Balestrini, Paula A</creatorcontrib><creatorcontrib>Abdelbaki, Ahmed</creatorcontrib><creatorcontrib>McCarthy, Afshan</creatorcontrib><creatorcontrib>Devito, Liani</creatorcontrib><creatorcontrib>Senner, Claire E</creatorcontrib><creatorcontrib>Chen, Alice E</creatorcontrib><creatorcontrib>Munusamy, Prabhakaran</creatorcontrib><creatorcontrib>Blakeley, Paul</creatorcontrib><creatorcontrib>Elder, Kay</creatorcontrib><creatorcontrib>Snell, Phil</creatorcontrib><creatorcontrib>Christie, Leila</creatorcontrib><creatorcontrib>Serhal, Paul</creatorcontrib><creatorcontrib>Odia, Rabi A</creatorcontrib><creatorcontrib>Sangrithi, Mahesh</creatorcontrib><creatorcontrib>Niakan, Kathy K</creatorcontrib><creatorcontrib>Fogarty, Norah M E</creatorcontrib><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>Development (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Balestrini, Paula A</au><au>Abdelbaki, Ahmed</au><au>McCarthy, Afshan</au><au>Devito, Liani</au><au>Senner, Claire E</au><au>Chen, Alice E</au><au>Munusamy, Prabhakaran</au><au>Blakeley, Paul</au><au>Elder, Kay</au><au>Snell, Phil</au><au>Christie, Leila</au><au>Serhal, Paul</au><au>Odia, Rabi A</au><au>Sangrithi, Mahesh</au><au>Niakan, Kathy K</au><au>Fogarty, Norah M E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcription factor-based transdifferentiation of human embryonic to trophoblast stem cells</atitle><jtitle>Development (Cambridge)</jtitle><addtitle>Development</addtitle><date>2024-09-01</date><risdate>2024</risdate><volume>151</volume><issue>17</issue><issn>0950-1991</issn><issn>1477-9129</issn><eissn>1477-9129</eissn><abstract>During the first week of development, human embryos form a blastocyst composed of an inner cell mass and trophectoderm (TE) cells, the latter of which are progenitors of placental trophoblast. 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| fulltext | fulltext |
| identifier | ISSN: 0950-1991 |
| ispartof | Development (Cambridge), 2024-09, Vol.151 (17) |
| issn | 0950-1991 1477-9129 1477-9129 |
| language | eng |
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| source | MEDLINE; Company of Biologists |
| subjects | Blastocyst - cytology Blastocyst - metabolism Cell Differentiation Cell Transdifferentiation Female GATA2 Transcription Factor - genetics GATA2 Transcription Factor - metabolism GATA3 Transcription Factor - genetics GATA3 Transcription Factor - metabolism Gene Expression Regulation, Developmental Human Embryonic Stem Cells - cytology Human Embryonic Stem Cells - metabolism Humans Pregnancy Techniques and Resources Transcription Factor AP-2 - genetics Transcription Factor AP-2 - metabolism Transcription Factors - genetics Transcription Factors - metabolism Trophoblasts - cytology Trophoblasts - metabolism |
| title | Transcription factor-based transdifferentiation of human embryonic to trophoblast stem cells |
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