The authors generated a patient-specific iPSC line from a family cohort carrying a hereditary atrial septal defect (ASD) mutation in GATA4 gene, as well as a hESC line carrying the isogenic T280M mutation using the CRISPR/Cas9 genome editing method. The GATA4-mutant iPSCs and ESCs were then differentiated into cardiomyocytes to model GATA4 mutation-associated ASD.
[Cardiovascular Research]
6606345
{6606345:WESDNY8X}
apa
50
1
162140
https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-74afdb8f61c3b3288ac143bd80ad1025%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22WESDNY8X%22%2C%22library%22%3A%7B%22id%22%3A6606345%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Ye%20et%20al.%22%2C%22parsedDate%22%3A%222021-05-06%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EYe%2C%20L.%2C%20Yu%2C%20Y.%2C%20Zhao%2C%20Z.-A.%2C%20Zhao%2C%20D.%2C%20Ni%2C%20X.%2C%20Wang%2C%20Y.%2C%20Fang%2C%20X.%2C%20Yu%2C%20M.%2C%20Wang%2C%20Y.%2C%20Tang%2C%20J.-M.%2C%20Chen%2C%20Y.%2C%20Shen%2C%20Z.%2C%20Lei%2C%20W.%2C%20%26amp%3B%20Hu%2C%20S.%20%282021%29.%20Patient-specific%20iPSC-derived%20cardiomyocytes%20reveal%20abnormal%20regulation%20of%20FGF16%20in%20a%20familial%20atrial%20septal%20defect.%20%3Ci%3ECardiovascular%20Research%3C%5C%2Fi%3E%2C%20%3Ci%3Ecvab154%3C%5C%2Fi%3E.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fcvr%5C%2Fcvab154%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fcvr%5C%2Fcvab154%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D6606345%26amp%3Bitem_key%3DWESDNY8X%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Patient-specific%20iPSC-derived%20cardiomyocytes%20reveal%20abnormal%20regulation%20of%20FGF16%20in%20a%20familial%20atrial%20septal%20defect%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lingqun%22%2C%22lastName%22%3A%22Ye%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22You%22%2C%22lastName%22%3A%22Yu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhen-Ao%22%2C%22lastName%22%3A%22Zhao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dandan%22%2C%22lastName%22%3A%22Zhao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xuan%22%2C%22lastName%22%3A%22Ni%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yong%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xing%22%2C%22lastName%22%3A%22Fang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Miao%22%2C%22lastName%22%3A%22Yu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yongming%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun-Ming%22%2C%22lastName%22%3A%22Tang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ying%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhenya%22%2C%22lastName%22%3A%22Shen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Lei%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shijun%22%2C%22lastName%22%3A%22Hu%22%7D%5D%2C%22abstractNote%22%3A%22Congenital%20heart%20disease%20%28CHD%29%20frequently%20occurs%20in%20newborns%20due%20to%20abnormal%20formation%20of%20the%20heart%20or%20major%20blood%20vessels.%20Mutations%20in%20the%20GATA4%20gene%2C%20which%20encodes%20GATA%20binding%20protein%204%2C%20are%20responsible%20for%20atrial%20septal%20defect%20%28ASD%29%2C%20a%20common%20CHD.%20This%20study%20aims%20to%20gain%20insights%20into%20the%20molecular%20mechanisms%20of%20CHD%20using%20human%20induced%20pluripotent%20stem%20cells%20%28iPSCs%29%20from%20a%20family%20cohort%20with%20ASD.Patient-specific%20iPSCs%20possess%20the%20same%20genetic%20information%20as%20the%20donor%20and%20can%20differentiate%20into%20various%20cell%20types%20from%20all%20three%20germ%20layers%20in%20vitro%2C%20thus%20presenting%20a%20promising%20approach%20for%20disease%20modeling%20and%20molecular%20mechanism%20research.%20Here%2C%20we%20generated%20a%20patient-specific%20iPSC%20line%20%28iPSC-G4T280M%29%20from%20a%20family%20cohort%20carrying%20a%20hereditary%20ASD%20mutation%20in%20GATA4%20gene%20%28T280M%29%2C%20as%20well%20as%20a%20human%20embryonic%20stem%20cell%20line%20%28ESC-G4T280M%29%20carrying%20the%20isogenic%20T280M%20mutation%20using%20the%20CRISPR%5C%2FCas9%20genome%20editing%20method.%20The%20GATA4-mutant%20iPSCs%20and%20ESCs%20were%20then%20differentiated%20into%20cardiomyocytes%20%28CMs%29%20to%20model%20GATA4%20mutation-associated%20ASD.%20We%20observed%20an%20obvious%20defect%20in%20cell%20proliferation%20in%20cardiomyocytes%20derived%20from%20both%20GATA4T280M-mutant%20iPSCs%20%28iPSC-G4T280M-CMs%29%20and%20ESCs%20%28ESC-G4T280M-CMs%29%2C%20while%20the%20impaired%20proliferation%20ability%20of%20iPSC-G4T280M-CMs%20could%20be%20restored%20by%20gene%20correction.%20Integrated%20analysis%20of%20RNA-Seq%20and%20ChIP-Seq%20data%20indicated%20that%20FGF16%20is%20a%20direct%20target%20of%20wild-type%20GATA4.%20However%2C%20the%20T280M%20mutation%20obstructed%20GATA4%20occupancy%20at%20the%20FGF16%20promoter%20region%2C%20leading%20to%20impaired%20activation%20of%20FGF16%20transcription.%20Overexpression%20of%20FGF16%20in%20GATA4-mutant%20cardiomyocytes%20rescued%20the%20cell%20proliferation%20defect.%20The%20direct%20relationship%20between%20GATA4T280M%20and%20ASD%20was%20demonstrated%20in%20a%20human%20iPSC%20model%20for%20the%20first%20time.In%20summary%2C%20our%20study%20revealed%20the%20molecular%20mechanism%20of%20the%20GATA4T280M%20mutation%20in%20ASD.%20Understanding%20the%20roles%20of%20the%20GATA4-FGF16%20axis%20in%20iPSC-CMs%20will%20shed%20light%20on%20heart%20development%20and%20provide%20novel%20insights%20for%20the%20treatment%20of%20ASD%20and%20other%20CHD%20disorders.%22%2C%22date%22%3A%22May%206%2C%202021%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1093%5C%2Fcvr%5C%2Fcvab154%22%2C%22ISSN%22%3A%220008-6363%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fcvr%5C%2Fcvab154%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222021-05-12T18%3A32%3A54Z%22%7D%7D%5D%7D
Ye, L., Yu, Y., Zhao, Z.-A., Zhao, D., Ni, X., Wang, Y., Fang, X., Yu, M., Wang, Y., Tang, J.-M., Chen, Y., Shen, Z., Lei, W., & Hu, S. (2021). Patient-specific iPSC-derived cardiomyocytes reveal abnormal regulation of FGF16 in a familial atrial septal defect. Cardiovascular Research, cvab154. https://doi.org/10.1093/cvr/cvab154 Cite
