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Biology subjects

Hamrud, E.

Publications and source records attributed to Hamrud, E..

2 recordsLinked to original sources

A gradient border model for cell fate decisions at the neural plate border

The vertebrate neural plate border is a transient territory located at the edge of the neural plate containing precursors for all ectodermal derivatives: the neural plate; neural crest; placodes; and epidermis. Elegant functional experiments in a range of vertebrate models have provided an in-depth understanding of gene regulatory interactions within the ectoderm. However, these experiments conducted at tissue level raise seemingly contradictory models for fate allocation of individual cells. Here, we carry out single cell RNA sequencing of chick ectoderm from primitive streak to neurulation stage, to explore cell state diversity and heterogeneity. We characterise the dynamics of gene modules containing key factors known to regulate ectodermal cell fates, allowing us to model the order in which these fates are specified. Furthermore, we find that genes previously classified as neural plate border specifiers typically exhibit dynamic expression patterns and are biased towards either placodal or neural crest fates, revealing that the neural plate border should be seen as an anatomical region of the ectoderm and not a discrete transcriptional state. Through co-expression of placodal and neural crest markers, we identify a population of border located unstable progenitors (BLUPs) which gradually reduces in size as fate segregation occurs. Considering our findings, we propose a gradient border model for cell fate choice at the neural plate border, with the probability of cell fate allocation closely tied to the spatiotemporal positioning of cells.

developmental biology↗

ILC1-derived TGFβ1 drives intestinal remodelling

Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we developed gut organoid co-cultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate for the first time that murine and human ILC1 secrete TGF{beta}1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.

immunology↗