Project ID NS-MH2024_05


Co Supervisor 1A Institute of Psychiatry, Psychology & Neuroscience, School of Neuroscience, Centre for Developmental NeurobiologyWebsite

Co Supervisor 1B Institute of Psychiatry, Psychology & Neuroscience, School of Neuroscience, Centre for Developmental NeurobiologyWebsite

Uncovering early gliogenesis in the developing human brain

Glial cells play vital roles in the development and function of the human brain, but we know surprisingly little about how they are generated during development. This includes key questions such as when and where glial cells are made, what their early functions are and how this differs from their functions in the adult brain.

This project will use cutting-edge human cell and tissue culture systems to investigate how glial cells are generated during human cortex development. We aim to uncover the identity of the glial cells generated early in development: their morphology, location, gene expression and function, and how these glial cells interact with the neurons and surrounding tissue, to generate a comprehensive characterisation of glial cells in the developing fetal brain.

It will take advantage of both laboratories’ expertise, combining the Berninger lab’s experience in human induced pluripotent stem cells (iPSC), organoid models and single cell OMICs with the Long lab’s experience in human fetal neocortex development and explant models. We will use a multidisciplinary approach, including live-imaging, transcriptome analysis and spatial transcriptomics, confocal-imaging and cell biology.

The student will investigate:

Year 1: Characterise glial cells in the early fetal brain, establish fetal explant cultures and iPSC/organoid cultures

Year 2: Analyse the transcriptomic identity of the glial cells in human brain development.

Year 3: Identify the function of glial cells in developing human brain in both typical and atypical development.

Representative Publications

Fan W, Jurado-Arjona J, Alanis-Lobato G et al., Berninger B. The transcriptional co-activator Yap1 promotes adult hippocampal neural stem cell activation. EMBO J 2023 Jun 1;42(11):e110384. doi: 10.15252/embj.2021110384.

Karow M, Camp JG, Falk S, et al., Berninger B. Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program. Nat Neurosci. July 2018. doi: 10.1038/s41593-018-0168-3.

Tiwari N, Pataskar A, Péron S, et al., Berninger B. Stage-Specific Transcription Factors Drive Astrogliogenesis by Remodeling Gene Regulatory Landscapes. Cell Stem Cell 2018 Oct 4;23(4):557-571.e8. doi: 10.1016/j.stem.2018.09.008.

Long KR, Newland B, Florio M, et al. Extracellular Matrix Components HAPLN1, Lumican, and Collagen I Cause Hyaluronic Acid-Dependent Folding of the Developing Human Neocortex. Neuron. July 2018. doi:10.1016/j.neuron.2018.07.013

Massimo M, Barelli C, Moreno C, Collesi C, Holloway R, Crespo B, Zentilin L, Williams AE, Miron VE, Giacca M, Long KR (2023) Haemorrhage of human fetal cortex associated with SARS-CoV-2 infection. Brain

Eigel D, Schuster R. Männel MJ, Thiele J, Panasiuk MJ, Andreae LC, Varricchio C, Brancale A, Welzel PB, Huttner WB, Werner C, Newland B, Long KR (2021). Sulfonated cryogel scaffolds for focal delivery in ex-vivo brain tissue cultures. Biomaterials doi: 10.1016/j.biomaterials.2021.120712