Crête neurale | EPFL Graph Search

La crête neurale ou plaque du toit désigne, chez l'embryon des craniates, une population de cellules transitoires et multipotentes générées à partir de la région la plus dorsale du tube neural. Ces cellules migrent dans l’ensemble de l'embryon au cours du développement et donnent naissance à une grande diversité de types cellulaires chez l'adulte. La crête neurale est à l'origine des mélanocytes (à l'exception des cellules pigmentaires de l'œil), d'une grande partie des os et des cartilages du squelette facial et du cou, de quelques cellules endocrines et donne naissance à toutes les cellules gliales et à la majeure partie des neurones du système nerveux périphérique. L'apparition de la crête neurale chez les vertébrés a probablement joué un rôle clé dans leur évolution, leur permettant notamment de devenir prédateur (la mandibule dérive de la crête neurale) et d'accroitre la taille de leur cerveau. Celui-ci aurait pu se développer, plus facilement que chez d'autres espèces, à l’int

Epithelial stem cells and mechanical signal transduction

Vincent Bernard Cattin

Hair follicles are cutaneous structures characteristic of mammals. These sensitive organs cycle and contain multipotent epithelial stem cells which are implicated in hair growth and hair cycle. A single whisker follicle of the rat hosts up to 1500 stem cells, many more than necessary to regenerate the entire follicle throughout the animal's life. These cells are preferentially located in the most innervated region of the hair follicle. We hypothesised that stem cells might have an additional function aside from tissue renewal: stem cells may be involved in the mechanical signal transduction between hair follicle and afferent nervous system. This supplemental role may either take place through the interaction of the multipotent epithelial stem cells with nerve endings, or through neuroepithelial Merkel cells acting as intermediates. Merkel cells are located in the basal layer of the whisker follicle outer root sheath (ORS) and share a close relationship with their neighbouring nerve endings. These cells specifically express the transcription factor Math1 and their function is poorly understood. We demonstrate here by clonal analysis and transplantation assays that Merkel cells are not derived from epithelial stem cells. In addition, Math1-expressing cells isolated from the epidermis are unable to form colonies and to participate in the generation epidermal lineages when transplanted, failing to show stemness properties. Furthermore, when cultured in conditions that favour the growth of neurospheres, they are unable to proliferate, revealing a different behaviour than that of skin-derived neural crest cells. We also demonstrate that multipotent epithelial stem cells express several proteins implicated in glutamate neurotransmission, as well as other molecules usually found in the nervous system. The expression of NMDAR and AMPAR subunits, as well as their scaffolding proteins and neurotransmitter vesicular transport-implicated proteins are uncovered for the first time in the multipotent epithelial stem cells from the bulge. Our results support the mechanical signal transduction hypothesis and confirm the increasingly important role of the recently described neural-like structures of the skin. This work paves the way for a better comprehension of multipotent epithelial stem cell behaviour and stem cell-related pathologies.

EPFL2008

RNA velocity of single cells

Gioele La Manno, Zehua Liu

RNA abundance is a powerful indicator of the state of individual cells. Single-cell RNA sequencing can reveal RNA abundance with high quantitative accuracy, sensitivity and throughput 1 . However, this approach captures only a static snapshot at a point in time, posing a challenge for the analysis of time-resolved phenomena such as embryogenesis or tissue regeneration. Here we show that RNA velocity—the time derivative of the gene expression state—can be directly estimated by distinguishing between unspliced and spliced mRNAs in common single-cell RNA sequencing protocols. RNA velocity is a high-dimensional vector that predicts the future state of individual cells on a timescale of hours. We validate its accuracy in the neural crest lineage, demonstrate its use on multiple published datasets and technical platforms, reveal the branching lineage tree of the developing mouse hippocampus, and examine the kinetics of transcription in human embryonic brain. We expect RNA velocity to greatly aid the analysis of developmental lineages and cellular dynamics, particularly in humans.

2018

Towards engineering an artificial neural tube

Jisoo Park

In this thesis, I present a self-organizing neural tube organoid that is strikingly similar in morphology, cell-type composition, and patterning to the mouse embryonic neural tube. When exposed to a sequence of epiblast culture conditions and neural differentiation conditions in 3D Matrigel, single mouse embryonic stem cells develop into spontaneously elongating neuroepithelial tissues organized with key hallmarks of the neural tube. Single cell transcriptomics revealed the presence of regionalized cell types spanning the region from the midbrain to the spinal cord along the AP axis of the embryo. In long-term culture experiments for organoid maturation, I observed the emergence of neural crest cells and mature neurons. Furthermore, I developed a microfluidics-based system to promote a similar DV patterning to a neural tube. Also, maturation of neural tube organoid exhibited the emergence and migration of multipotent neural crest cells. Collectively, the accessibility and scalability of these organoids make them a unique model of the developing neural tube, allowing the study of key mechanisms involved in striking morphogenesis by self-organization, cell regionalization, neural crest development, and morphogen-triggered patterning in vivo.

EPFL2021

Epithelial stem cells and mechanical signal transduction

Vincent Bernard Cattin

EPFL2008