Location

IBB 2316

In partial fulfillment of the requirements for the degree of

 

Doctor of Philosophy in Biology

In the

School of Biological Sciences

 

Ruiqiao Yang

 

Will defend her dissertation

 

ROLE OF H1 LINKER HISTONES IN GASTRULOID DEVELOPMENT

 

Time and Date: 1:00PM (Eastern Time), July 9th, 2026

Location: IBB 2316

 

 Thesis Advisor:

Yuhong Fan, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

 

Committee Members:

Mirjana M. Brockett, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

 

Francesca Storici, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

 

Rabindranath De La Fuente, Ph.D.

    Department of Physiology and Pharmacology

University of Georgia

 

Jiyue Zhu, Ph.D.

       School of Pharmacy and Pharmaceutical Sciences

    Washington State University

 

ABSTRACT: H1 Linker histones are key chromatin proteins that bind to nucleosomes and linker DNA, facilitating the folding of higher-order chromatin structures. Linker histone H1 is essential for mammalian embryogenesis, and its depletion has been shown to impair embryonic stem cell differentiation. To dissect the role of H1 histones in coordinating developmental programs during embryogenesis, we first optimized a protocol for generating gastruloids, an in vitro 3D organoid model of gastrulation, from mouse embryonic stem cells (ESCs). By modeling gastruloid development and leveraging H1c/H1d/H1e triple-knockout (H1 TKO) ESCs, we investigated how H1 regulates developmental patterning and programming. Compared with wild-type gastruloids, H1 TKO gastruloids exhibited markedly impaired growth and temporal patterning and lacked clear axial organization and beating cardiomyocytes. Transcriptomic analysis of gastruloids by RNA sequencing revealed extensive changes in gene expression, with enrichment in multiple developmental programs and signaling processes, including myogenesis, epithelial–mesenchymal transition, hypoxia, glycolysis, and other signaling pathways. H1 depletion resulted in the dysregulation of genes associated with diverse developmental processes, including morphogenesis, muscle and heart development, nervous system development, and chromosome organization. These results demonstrate that H1 is required for the proper activation of multiple developmental programs during gastruloid formation and underscore the essential role of H1 in coordinating cell differentiation, migration, and morphogenesis during embryogenesis.