Multi-omics characterization of human Embryonic Stem Cells-derived Pharyngeal Endoderm cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE208319 | GEO | 2022/07/20
REPOSITORIES: GEO
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Project description:We have developed a novel in vitro protocol for the derivation of bona fide Pharyngeal Endoderm (PE) cells from hESCs. We demonstrated that our PE cells robustly express Pharyngeal Endoderm markers, they are transcriptionally similar to PE cells isolated from in vivo mouse development and represent a transcriptionally homogeneous population. Importantly, we elucidated the contribution of Retinoic Acid in promoting a transcriptional and epigenetic rewiring of PE cells. In addition, we defined the epigenetic landscape of PE cells by combining ATAC-Seq and ChIP-Seq of histone marks.
2022-07-20 | GSE206568 | GEO
Project description:We have developed a novel in vitro protocol for the derivation of bona fide Pharyngeal Endoderm (PE) cells from hESCs. We demonstrated that our PE cells robustly express Pharyngeal Endoderm markers, they are transcriptionally similar to PE cells isolated from in vivo mouse development and represent a transcriptionally homogeneous population. Importantly, we elucidated the contribution of Retinoic Acid in promoting a transcriptional and epigenetic rewiring of PE cells. In addition, we defined the epigenetic landscape of PE cells by combining ATAC-Seq and ChIP-Seq of histone marks.
2022-07-20 | GSE206567 | GEO
Project description:We have developed a novel in vitro protocol for the derivation of bona fide Pharyngeal Endoderm (PE) cells from hESCs. We demonstrated that our PE cells robustly express Pharyngeal Endoderm markers, they are transcriptionally similar to PE cells isolated from in vivo mouse development and represent a transcriptionally homogeneous population. Importantly, we elucidated the contribution of Retinoic Acid in promoting a transcriptional and epigenetic rewiring of PE cells. In addition, we defined the epigenetic landscape of PE cells by combining ATAC-Seq and ChIP-Seq of histone marks.
2022-07-20 | GSE208317 | GEO
Project description:We have developed a novel in vitro protocol for the derivation of bona fide Pharyngeal Endoderm (PE) cells from hESCs. We demonstrated that our PE cells robustly express Pharyngeal Endoderm markers, they are transcriptionally similar to PE cells isolated from in vivo mouse development and represent a transcriptionally homogeneous population. Importantly, we elucidated the contribution of Retinoic Acid in promoting a transcriptional and epigenetic rewiring of PE cells. In addition, we defined the epigenetic landscape of PE cells by combining ATAC-Seq and ChIP-Seq of histone marks.
2022-07-20 | GSE206566 | GEO
Project description:Normal commitment of the endoderm of the third pharyngeal pouch (3PP) is essential for the development and differentiation of the thymus. The aim of this study was to investigate the role of transcription factor HOXA3 in the development and differentiation of the third pharyngeal pouch endoderm from human embryonic stem cells (hESCs). 3PP endoderm (3PPE) was differentiated from hESC-derived definitive endoderm (DE) by mimicking developmental queues with Activin A, WNT3A, retinoic acid and BMP4. The function of 3PPE was assessed by further differentiating into functional thymic epithelial cells. The effect of HOXA3 inhibition on cells of 3PPE was subsequently investigated. A highly efficient approach for differentiating 3PPE cells has been developed and these cells expressed 3PPE related genes HOXA3, SIX1, PAX9 as well as EpCAM. 3PPE cells had a strong potential to develop into thymic epithelia which expressed both the cortical epithelial cell markers K8 and CD205, and the medullary epithelial cell markers K5 and AIRE, and also promoted T cell maturation. More importantly, transcription factor HOXA3 not only regulated the differentiation of 3PPE, but also had a crucial role for the proliferation and migration 3PPE cells. Our further investigation revealed that HOXA3 controlled the commitment and function of 3PPE through the regulation of the Wnt signaling pathway by EPHB2. Our results demonstrated that HOXA3 functioned as the on-off switch to regulate the development of hESC-derived 3PPE through EPHB2-mediated Wnt pathway, and our findings will provide new insights into studying the development of the third pharyngeal pouch and thymic organ in vitro and in vivo.
2023-07-24 | GSE237751 | GEO
Project description:Developmental defects affecting the pharynx and derived tissues can be found in a variety of syndromes, including DiGeorge, 22q11 deletion, CHARGE and Otofaciocervical syndromes. The associated malformations and dysfunctions of pharynx-derived tissues precipitate phenotypes ranging from malformed features and endocrine disorders to severe immunodeficiency, some of which are associated with high morbidity or elaborate treatment and health care costs. While some of the developmental defects have been linked to mutations or single-nucleotide polymorphisms in transcription factors (TFs) or cis-regulatory elements (CREs), the origin of most pharynx-specific birth defects remain poorly understood and the underlying genetic causes as well as epigenetic context remain elusive. Unfortunately, restricted human tissue access, and discordance of genetic factor requirement and phenotypic penetrance of disease associated human mutations when modeled in mice, has prohibited detailed insights on the molecular basis of mentioned human diseases. Human pluripotent stem cells (hPSCs) could in principle allow for detailed a genetically tractable model to decipher the molecular logic of normal and impaired pharynx development. To unlock hPSC for investigation of pharyngeal malformations and ensuing syndromes, we have developed a differentiation protocol to generate human pharyngeal endoderm in vitro. We have applied multi-omic approaches to characterize the molecular logic of cell fate transitions and developed models of gene regulatory network activities.
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Project description:Developmental defects affecting the pharynx and derived tissues can be found in a variety of syndromes, including DiGeorge, 22q11 deletion, CHARGE and Otofaciocervical syndromes. The associated malformations and dysfunctions of pharynx-derived tissues precipitate phenotypes ranging from malformed features and endocrine disorders to severe immunodeficiency, some of which are associated with high morbidity or elaborate treatment and health care costs. While some of the developmental defects have been linked to mutations or single-nucleotide polymorphisms in transcription factors (TFs) or cis-regulatory elements (CREs), the origin of most pharynx-specific birth defects remain poorly understood and the underlying genetic causes as well as epigenetic context remain elusive. Unfortunately, restricted human tissue access, and discordance of genetic factor requirement and phenotypic penetrance of disease associated human mutations when modeled in mice, has prohibited detailed insights on the molecular basis of mentioned human diseases. Human pluripotent stem cells (hPSCs) could in principle allow for detailed a genetically tractable model to decipher the molecular logic of normal and impaired pharynx development. To unlock hPSC for investigation of pharyngeal malformations and ensuing syndromes, we have developed a differentiation protocol to generate human pharyngeal endoderm in vitro. We have applied multi-omic approaches to characterize the molecular logic of cell fate transitions and developed models of gene regulatory network activities.
2023-08-17 | GSE222442 | GEO
Project description:Developmental defects affecting the pharynx and derived tissues can be found in a variety of syndromes, including DiGeorge, 22q11 deletion, CHARGE and Otofaciocervical syndromes. The associated malformations and dysfunctions of pharynx-derived tissues precipitate phenotypes ranging from malformed features and endocrine disorders to severe immunodeficiency, some of which are associated with high morbidity or elaborate treatment and health care costs. While some of the developmental defects have been linked to mutations or single-nucleotide polymorphisms in transcription factors (TFs) or cis-regulatory elements (CREs), the origin of most pharynx-specific birth defects remain poorly understood and the underlying genetic causes as well as epigenetic context remain elusive. Unfortunately, restricted human tissue access, and discordance of genetic factor requirement and phenotypic penetrance of disease associated human mutations when modeled in mice, has prohibited detailed insights on the molecular basis of mentioned human diseases. Human pluripotent stem cells (hPSCs) could in principle allow for detailed a genetically tractable model to decipher the molecular logic of normal and impaired pharynx development. To unlock hPSC for investigation of pharyngeal malformations and ensuing syndromes, we have developed a differentiation protocol to generate human pharyngeal endoderm in vitro. We have applied multi-omic approaches to characterize the molecular logic of cell fate transitions and developed models of gene regulatory network activities.
2023-08-17 | GSE222441 | GEO
Project description:Developmental defects affecting the pharynx and derived tissues can be found in a variety of syndromes, including DiGeorge, 22q11 deletion, CHARGE and Otofaciocervical syndromes. The associated malformations and dysfunctions of pharynx-derived tissues precipitate phenotypes ranging from malformed features and endocrine disorders to severe immunodeficiency, some of which are associated with high morbidity or elaborate treatment and health care costs. While some of the developmental defects have been linked to mutations or single-nucleotide polymorphisms in transcription factors (TFs) or cis-regulatory elements (CREs), the origin of most pharynx-specific birth defects remain poorly understood and the underlying genetic causes as well as epigenetic context remain elusive. Unfortunately, restricted human tissue access, and discordance of genetic factor requirement and phenotypic penetrance of disease associated human mutations when modeled in mice, has prohibited detailed insights on the molecular basis of mentioned human diseases. Human pluripotent stem cells (hPSCs) could in principle allow for detailed a genetically tractable model to decipher the molecular logic of normal and impaired pharynx development. To unlock hPSC for investigation of pharyngeal malformations and ensuing syndromes, we have developed a differentiation protocol to generate human pharyngeal endoderm in vitro. We have applied multi-omic approaches to characterize the molecular logic of cell fate transitions and developed models of gene regulatory network activities.
2023-08-17 | GSE222439 | GEO
Project description:Developmental defects affecting the pharynx and derived tissues can be found in a variety of syndromes, including DiGeorge, 22q11 deletion, CHARGE and Otofaciocervical syndromes. The associated malformations and dysfunctions of pharynx-derived tissues precipitate phenotypes ranging from malformed features and endocrine disorders to severe immunodeficiency, some of which are associated with high morbidity or elaborate treatment and health care costs. While some of the developmental defects have been linked to mutations or single-nucleotide polymorphisms in transcription factors (TFs) or cis-regulatory elements (CREs), the origin of most pharynx-specific birth defects remain poorly understood and the underlying genetic causes as well as epigenetic context remain elusive. Unfortunately, restricted human tissue access, and discordance of genetic factor requirement and phenotypic penetrance of disease associated human mutations when modeled in mice, has prohibited detailed insights on the molecular basis of mentioned human diseases. Human pluripotent stem cells (hPSCs) could in principle allow for detailed a genetically tractable model to decipher the molecular logic of normal and impaired pharynx development. To unlock hPSC for investigation of pharyngeal malformations and ensuing syndromes, we have developed a differentiation protocol to generate human pharyngeal endoderm in vitro. We have applied multi-omic approaches to characterize the molecular logic of cell fate transitions and developed models of gene regulatory network activities.
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