Publication highlights

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Explore a selection of research case studies from the past five years.

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Intro

Researchers at the Crick are tackling the big questions about human health and disease, and new findings are published every week.

Our faculty have picked some of the most significant papers published by Crick scientists, all of which are freely available thanks to our open science policy.

Highlights

Human Embryonic Stem Cells responding to different combinations of cues and forming different fates.

Converging development: how cell paths unite to build tissues

Several models of cell fate lineages have been presented, some proposing a traditional straight path and others a more dynamic model, where cell fate remains more flexible. Researchers at the Crick combined a range of experimental techniques - single cell transcriptomics, quantitative live cell imaging and mathematical modelling - to track cell fate and determine which path is the right one. They found that there was no singular path, and these theories were not competing explanations but complementary snapshots of human development. The team also observed the influence of two important signalling molecules, Activin and BMP4, in determining which route cells would take between mesoderm or endoderm layers.

Combinatorial BMP4 and activin direct the choice between alternate routes to endoderm in a stem cell model of human gastrulation

Published in Developmental Cell

Published

PGAs with two different cell populations

New stem cell model sheds light on human amniotic sac development

Researchers at the Francis Crick Institute have developed a new stem cell model of the mature human amniotic sac, which replicates development of the tissues supporting the embryo from two to four weeks after fertilisation. The new 3D model – called a post-gastrulation amnioid (PGA) – closely resembles the human amnion and other supportive tissues after gastrulation. The team developed PGAs by culturing human embryonic stem cells in a series of steps with just two chemical signals over 48 hours, after which the cells organised themselves into the inner and outer layers of the amnion. A sac-like structure formed by day 10 in over 90% of the PGAs, which expanded in size over 90 days. The researchers showed that a transcription factor called GATA3 is necessary to kick-start amnion development and that signals from the amnion can communicate with embryonic cells to stimulate growth. Finally, they believe PGAs could also provide an alternative source of amniotic membranes for medical procedures like cornea reconstruction.

Post-gastrulation amnioids as a stem cell-derived model of human extra-embryonic development

Published in Cell

Published

Image showing colonies of cells, showing differentiation in the first germ layers.

GATA3 mediates a fast, irreversible commitment to BMP4-driven differentiation in human embryonic stem cells

This manuscript was the first demonstration that irreversible commitment to cellular differentiation during early development happens unexpectedly early. The paper reflects our interdisciplinary work, combining single cell imaging, mathematical modelling and -omics approaches. We discovered a new class of genes which we termed early commitment genes (ECG) that are responsible for the pluripotency-to-differentiation transition. It was also our first manuscript in developmental biology, a new field outside of our lab’s expertise.

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Published in Cell Stem Cell

Published