GATA6-AS1 Regulates GATA6 Expression to Modulate Human Endoderm Differentiation.

Abstract:

:Transcriptome analysis has uncovered a series of long noncoding RNAs (lncRNAs) transcribed during cell differentiation, but how lncRNA is integrated with known transcriptional regulatory network is poorly understood. Here, we utilize human definitive endoderm differentiation as a model system and decipher the functional interaction between lncRNA and key transcriptional factor. We have identified GATA6-AS1, an lncRNA divergently transcribed from the GATA6 locus, is highly expressed during endoderm differentiation. Knockdown of GATA6-AS1 in human pluripotent stem cells has no influence on morphology and pluripotency; however, GATA6-AS1 depletion causes the deficiency of definitive endoderm differentiation. GATA6-AS1 positively regulates the expression of endoderm key factor GATA6. Further investigation shows GATA6-AS1 interacts with SMAD2/3 and activates the transcription of GATA6. In addition, overexpression of GATA6 is able to rescue the defect of endoderm differentiation due to the absence of GATA6-AS1, suggesting that GATA6 is the functional target of GATA6-AS1 during endoderm differentiation. Ultimately, our study reveals that GATA6-AS1 is necessary for human endoderm specification and reveals the underlying mechanism between GATA6-AS1 and GATA6.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Yang J,Lu P,Li M,Yan C,Zhang T,Jiang W

doi

10.1016/j.stemcr.2020.07.014

subject

Has Abstract

pub_date

2020-09-08 00:00:00

pages

694-705

issue

3

issn

2213-6711

pii

S2213-6711(20)30291-5

journal_volume

15

pub_type

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