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Updated: Oct 5, 2025
Genome-wide Snapshot of Chromatin Regulators and States in Xenopus Embryos by ChIP-Seq
Published on: February 26, 2015
Integration of single-cell transcriptomes and chromatin landscapes reveals regulatory programs driving pharyngeal
Margaret E Magaletta1,2, Macrina Lobo1,2, Eric M Kernfeld1,2
1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Insights
Maldevelopment of the pharyngeal endoderm causes human disorders. This study maps gene regulatory networks driving its development, revealing insights into developmental diseases.
Area of Science:
- Developmental Biology
- Genomics
- Molecular Biology
Background:
- Pharyngeal endoderm maldevelopment contributes to human developmental disorders.
- Current understanding of gene regulatory networks (GRNs) driving pharyngeal endoderm development is incomplete.
- Existing genetic data does not fully explain the spectrum of associated phenotypes.
Purpose of the Study:
- To create a comprehensive, multi-omic developmental resource for pharyngeal endoderm.
- To elucidate the molecular basis and GRNs governing pharyngeal endoderm development.
- To characterize the role of specific transcription factors in this process.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) for transcriptomic profiling.
- Single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) for chromatin accessibility.
- Integration of multi-omic data in developing mouse embryos.
Main Results:
- Identification of cell-type specific gene regulation during pharyngeal endoderm development.
- Distillation of GRN models defining developing organ domains.
- Characterization of an immunodeficiency-associated forkhead box transcription factor's role.
Conclusions:
- This study provides an integrated multi-omic map of pharyngeal endoderm development.
- The findings offer insights into the molecular drivers of developmental syndromes.
- The characterized transcription factor is implicated in pharyngeal development and immunodeficiency.
Abstract:
Maldevelopment of the pharyngeal endoderm, an embryonic tissue critical for patterning of the pharyngeal region and ensuing organogenesis, ultimately contributes to several classes of human developmental syndromes and disorders. Such syndromes are characterized by a spectrum of phenotypes that currently cannot be fully explained by known mutations or genetic variants due to gaps in characterization of critical drivers of normal and dysfunctional development. Despite the disease-relevance of pharyngeal endoderm, we still lack a comprehensive and integrative view of the molecular basis and gene regulatory networks driving pharyngeal endoderm development. To close this gap, we apply transcriptomic and chromatin accessibility single-cell sequencing technologies to generate a multi-omic developmental resource spanning pharyngeal endoderm patterning to the emergence of organ-specific epithelia in the developing mouse embryo. We identify cell-type specific gene regulation, distill GRN models that define developing organ domains, and characterize the role of an immunodeficiency-associated forkhead box transcription factor.
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