Ep. 279: “Direct Reprogramming” Featuring Dr. Samantha Morris
Oct 22, 2024
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Dr. Samantha Morris, an Associate Professor at Brigham and Women’s Hospital and Harvard Medical School, dives into the fascinating world of gene regulatory networks and cell identity. She shares her groundbreaking work on manipulating genetic pathways and measuring cell fate transitions. The discussion highlights the complexities of direct reprogramming and innovative tools like CellNet. Additionally, she emphasizes the importance of collaboration in stem cell research and reflects on the evolving landscape of funding and mentorship in the scientific community.
Dr. Samantha Morris emphasizes the complexity of direct reprogramming, highlighting the need to understand gene regulatory networks for cell identity transformation.
Recent studies uncover the vital role of immune cells, especially macrophages, in skin development and their involvement in hair follicle formation and wound healing.
Morris's lab's innovative lineage tracing techniques show distinct reprogramming trajectories, revealing insights that could enhance the effectiveness of cell identity engineering.
Deep dives
Direct Reprogramming and Cell Identity
Research on direct reprogramming emphasizes the complexity of changing one cell type into another. Dr. Samantha Morris discusses how initially it appeared simple to force cell identity switches through transcription factors. However, her work has revealed that this reprogramming process is not straightforward, often requiring an understanding of the underlying gene regulatory networks that define cell identity. As a result, identifying the precise mechanisms and pathways involved in cell fate determination has become critical for improving reprogramming efficiency and effectiveness.
Role of Immune Cells in Development
A recent study highlights the previously underappreciated role of immune cells, particularly macrophages, in skin morphogenesis. Researchers constructed a comprehensive atlas of prenatal human skin, demonstrating that macrophages not only participate in immune responses but also play a crucial role in regulating skin development through interactions with non-immune cells. This crosstalk is essential for the formation of hair follicles and enables scarless wound healing, pointing to the significance of immune cells in shaping developmental processes beyond their traditional immune functions. The findings suggest new avenues for exploring how immune cells contribute to other developmental contexts.
Innovations in Lineage Tracing
Dr. Morris's lab has developed advanced lineage tracing techniques using a tool called CellTag, which allows for capturing cellular barcodes during the reprogramming process. This method has enabled researchers to investigate the earliest changes that dictate a cell's fate during reprogramming. Study outcomes reveal two distinct trajectories: one leading to functional reprogramming and another termed the 'dead end,' which fails to fully reprogram cells. By understanding these pathways, researchers aim to enhance the efficiency and accuracy of cell identity engineering, ultimately improving therapeutic applications.
High-Throughput Screening for Cardiac Fibrosis
Recent research from the Wu lab has focused on identifying new therapeutic targets for cardiac fibrosis through high-throughput screening using induced pluripotent stem cell (iPSC)-derived cardiac fibroblasts. The study emphasizes the role of a compound called artesunate which showed efficacy in reducing cardiac fibrosis and improving heart function in animal models. By utilizing sophisticated modeling systems and advanced screening techniques, the team has pinpointed the myeloid differentiation factor MD2 as a potential target, enhancing therapeutic development for a condition that lacks effective treatments. This study illustrates the potential of integrating iPSC technology with high-throughput approaches to address significant medical needs.
Metabolics in Embryonic Development
Emerging research has revisited the concept of metabolic gradients in developmental biology, connecting metabolic processes to cellular fate decisions. A study led by Dr. Burna Sozin revealed that glucose metabolism plays a critical role during gastrulation in mouse embryos, linking metabolic activity to mechanistic pathways that drive tissue patterning. The research demonstrates how metabolic states influence developmental processes, contributing to the broader understanding of how nutrient processing affects embryonic development. This work underscores the importance of further exploring metabolic mechanisms in both developmental biology and regenerative medicine.
Dr. Samantha Morris is an Associate Professor of Medicine at Brigham and Women’s Hospital and Associate Professor of Systems Biology at Harvard Medical School. She talks about dissecting and manipulating the genetic pathways that regulate cell identity. She discusses tools to measure cell fate transitions and incorporating in silico and in vitro experiments.
A Prenatal Skin Atlas – A skin atlas revealed that crosstalk between non-immune and immune cells underpins the formation of hair follicles.
Human Pancreatic Differentiation – Researchers used single-nucleus RNA sequencing to characterize the human fetal pancreatic microenvironment.
A Cardiac Fibrosis Therapeutic Target – High-throughput screening in iPSC-derived cardiac fibroblasts identified MD2 as a therapeutic target for cardiac fibrosis.
Mammalian Gastrulation – Scientists identified a link between the pathways that produce energy for embryo growth and the systems that regulate cell specialization.
