HnRNPA2B1 promotes osteogenesis differentiation of human adipose-derived stem cells through PHC2/GATA6/BMP axis [CUT&RUN]
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PROVIDER: PRJNA1232150 | ENA |
REPOSITORIES: ENA
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Project description:m6A modification is prevalent on messenger RNA and plays a crucial role in various eukaryotic biological processes, including growth, development, disease, and aging. hnRNPA2B1, a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family, has been identified as an m6A reader. In this study, hnRNPA2B1 was shown to promote osteogenesis differentiation of human adipose-derived stem cells (hASCs) in vitro. Furthermore, the overexpression of hnRNPA2B1 facilitated bone defect healing in in vivo models of bone defects. hnRNPA2B1 RIP-seq, mRNA-seq, and MERIP-seq were used to identify PHC2 as the target gene of hnRNPA2B1. hnRNPA2B1 enhances the stability of PHC2 mRNA through m6A regulation. PHC2 binds to the promoter region of GATA6 and represses GATA6 expression by increasing H3K27me3 levels. GATA6, in turn, inhibits BMP signaling pathways and the osteogenesis differentiation of hASCs. hnRNPA2B1-PHC2-GATA6-BMP axis offers a promising perspective for the development of stem cell based bone tissue engineering.
2025-03-10 | GSE291175 | GEO
Project description:m6A modification is prevalent on messenger RNA and plays a crucial role in various eukaryotic biological processes, including growth, development, disease, and aging. hnRNPA2B1, a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family, has been identified as an m6A reader. In this study, hnRNPA2B1 was shown to promote osteogenesis differentiation of human adipose-derived stem cells (hASCs) in vitro. Furthermore, the overexpression of hnRNPA2B1 facilitated bone defect healing in in vivo models of bone defects. hnRNPA2B1 RIP-seq, mRNA-seq, and MERIP-seq were used to identify PHC2 as the target gene of hnRNPA2B1. hnRNPA2B1 enhances the stability of PHC2 mRNA through m6A regulation. PHC2 binds to the promoter region of GATA6 and represses GATA6 expression by increasing H3K27me3 levels. GATA6, in turn, inhibits BMP signaling pathways and the osteogenesis differentiation of hASCs. hnRNPA2B1-PHC2-GATA6-BMP axis offers a promising perspective for the development of stem cell based bone tissue engineering.
2025-03-10 | GSE291171 | GEO
Project description:hnRNPA2B1 promotes osteogenesis differentiation of human adipose-derived stem cells through PHC2/GATA6/BMP axis [RIP-seq]
| PRJNA1232143 | ENA
Project description:Haploinsufficiency for GATA6 is associated with congenital heart disease (CHD) with variable comorbidity of pancreatic or diaphragm defects, although the etiology of disease is not well understood. Here, we used cardiac directed differentiation from human embryonic stem cells (hESCs) as a platform to study GATA6 function during early cardiogenesis. GATA6 loss-of-function hESCs had a profound impairment in cardiac progenitor cell (CPC) specification and cardiomyocyte (CM) generation due to early defects during the mesendoderm and lateral mesoderm patterning stages. Profiling by RNA-seq and CUT&RUN identified genes of the WNT and BMP programs regulated by GATA6 during early mesoderm patterning. Furthermore, interactome analysis detected GATA6 binding with developmental transcription factors and chromatin remodelers suggesting cooperative regulation of cardiac lineage gene accessibility. We show that modulating WNT and BMP inputs during the first 48 hours of cardiac differentiation is sufficient to partially rescue CPC and CM defects in GATA6 heterozygous and homozygous mutant hESCs. This study provides evidence of the regulatory functions for GATA6 directing human precardiac mesoderm patterning during the earliest stages of cardiogenesis to further our understanding of haploinsufficiency causing CHD and the co-occurrence of cardiac and other organ defects caused by human GATA6 mutations.
2024-08-27 | GSE275685 | GEO
Project description:Haploinsufficiency for GATA6 is associated with congenital heart disease (CHD) with variable comorbidity of pancreatic or diaphragm defects, although the etiology of disease is not well understood. Here, we used cardiac directed differentiation from human embryonic stem cells (hESCs) as a platform to study GATA6 function during early cardiogenesis. GATA6 loss-of-function hESCs had a profound impairment in cardiac progenitor cell (CPC) specification and cardiomyocyte (CM) generation due to early defects during the mesendoderm and lateral mesoderm patterning stages. Profiling by RNA-seq and CUT&RUN identified genes of the WNT and BMP programs regulated by GATA6 during early mesoderm patterning. Furthermore, interactome analysis detected GATA6 binding with developmental transcription factors and chromatin remodelers suggesting cooperative regulation of cardiac lineage gene accessibility. We show that modulating WNT and BMP inputs during the first 48 hours of cardiac differentiation is sufficient to partially rescue CPC and CM defects in GATA6 heterozygous and homozygous mutant hESCs. This study provides evidence of the regulatory functions for GATA6 directing human precardiac mesoderm patterning during the earliest stages of cardiogenesis to further our understanding of haploinsufficiency causing CHD and the co-occurrence of cardiac and other organ defects caused by human GATA6 mutations.
2024-08-27 | GSE275686 | GEO
Project description:Aberrant activation of WNT signaling and loss of BMP signals represent the two main alterations leading to the initiation of colorectal cancer (CRC). Here we screen for genes required for maintaining the tumor stem cell phenotype and identify the zinc-finger transcription factor GATA6 as key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of LGR5 in adenoma stem cells while it restricts BMP signaling to differentiated tumor cells. Genetic deletion of Gata6 in mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumor stem cells. In human tumors, GATA6 represses BMP4 gene expression through binding to a regulatory region that has been previously linked to increased susceptibility to develop CRC. Thus, GATA6 creates a permissive environment for tumor stem cell expansion by controlling the major signaling pathways that influence CRC initiation.
2014-06-19 | GSE49479 | GEO
Project description:Aberrant activation of WNT signaling and loss of BMP signals represent the two main alterations leading to the initiation of colorectal cancer (CRC). Here we screen for genes required for maintaining the tumor stem cell phenotype and identify the zinc-finger transcription factor GATA6 as key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of LGR5 in adenoma stem cells while it restricts BMP signaling to differentiated tumor cells. Genetic deletion of Gata6 in mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumor stem cells. In human tumors, GATA6 represses BMP4 gene expression through binding to a regulatory region that has been previously linked to increased susceptibility to develop CRC. Thus, GATA6 creates a permissive environment for tumor stem cell expansion by controlling the major signaling pathways that influence CRC initiation. Total RNA from biological replicates of VillinCreERT2Gata6+/+Apcfl/fl and VillinCreERT2Gata6fl/flApcfl/fl colon adenoma tumor organoids grown for one week in control media (see growth protocol).Total RNA was extracted using the TRIzolM-BM-. Plus RNA Purification Kit (Life Technologies).
2014-06-19 | E-GEOD-49479 | biostudies-arrayexpress
Project description:To identify HNRNPA2B1 binding sites on endogenous nuclear RNAs, we performed HITS-CLIP for endogenous HNRNPA2B1 and RNA-seq to analyze the nuclear RNA under either METTL3 or HNRNPA2B1 depletion. Wild type MDA-MB-231 cells were subjected to the HITS-CLIP procedure on immunoprecipitated HNRNPA2B1 associated RNA obtained from the nuclear fraction (Licatalosi D, et al. 2008, Nature 456:464-U22). For RNA-seq, nuclear RNA was extracted from MDA-MB-231 or Hela cells knocked down for METTL3 or HNRNPA2B1.
2015-06-20 | E-GEOD-70061 | biostudies-arrayexpress
Project description:GATA6 regulates WNT and BMP programs to pattern precardiac mesoderm during the earliest stages of human cardiogenesis (CUT&RUN)
| PRJNA1152570 | ENA
Project description:Aberrant activation of WNT signaling and loss of BMP signals represent the two main alterations leading to the initiation of colorectal cancer (CRC). Here we screen for genes required for maintaining the tumor stem cell phenotype and identify the zinc-finger transcription factor GATA6 as key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of LGR5 in adenoma stem cells while it restricts BMP signaling to differentiated tumor cells. Genetic deletion of Gata6 in mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumor stem cells. In human tumors, GATA6 competes with beta-catenin/TCF4 for binding to a distal regulatory region of the BMP4 locus that has been previously linked to increased susceptibility to develop CRC. Hence, GATA6 creates a permissive environment for tumor stem cell expansion by controlling the major signaling pathways that influence CRC initiation.
2014-05-20 | GSE56895 | GEO