Morphogenesis | EPFL Graph Search

Morphogenesis (from the Greek morphê shape and genesis creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of developmental biology along with the control of tissue growth and patterning of cellular differentiation. The process controls the organized spatial distribution of cells during the embryonic development of an organism. Morphogenesis can take place also in a mature organism, such as in the normal maintenance of tissue by stem cells or in regeneration of tissues after damage. Cancer is an example of highly abnormal and pathological tissue morphogenesis. Morphogenesis also describes the development of unicellular life forms that do not have an embryonic stage in their life cycle. Morphogenesis is essential for the evolution of new forms. Morphogenesis is a mechanical process involving forces that generate mechanical stress, strain, and movement of cells, and

Deciphering the subcapsular epithelial cells in human fetal and postnatal thymus

Diane Sophie Elodie Hemon

Most papers related to thymus focus on the cortical and medullary epithelial cells whereas the subcapsular layer is ignored. In this thesis, we are providing new informations about the subcapsular thymic epithelial cells (TECs) by comparing them to cortical TECs, medullary TECs, Hassall's corpuscles (HCs) and the epidermis. We have demonstrated that TECs located in the subcapsular region are polarized cells adhering to an organized basement membrane and that they are interconnected in a tridimensional meshwork with all other TECs, including the TECs located in the HCs. We have confirmed that the thymus epithelium has a highly complex architecture that looks like no other epithelium. The 3D structure is certainly important for thymus functionality. However, how the 3D structure impacts T cell instruction remains to be investigated. Additionally, we have demonstrated that the subcapsular TECs express the surface marker EPCAM. Therefore, subcapsular TECs are part of the sorted EPCAM+ TEC population. We have also investigated the expression of proteins important for epidermal morphogenesis and we have unraveled strong similarities between the development of thymic epithelial cells and epidermis. Furthermore, we have shown that epithelial clusters of TP63 positive and Ki67 positive cells are present in the fetal subcortical region. Our work emphasizes that subcapsular TECs are important components of the thymic epithelial network and that they warrant further investigation.

EPFL2017

Engineering next generation organoids through guided stem cell self-organisation

Mikhail Nikolaev

One of the long-standing goals in the field of tissue engineering is the fabrication of de novo tissues or even organs to provide better tissue models for basic research and drug discovery, and to alleviate a shortage of donor organs in the future. Research in recent decades to understand tissue biology has led to the discovery of stem cell niches and the development of innovative protocols for the generation of three-dimensional in vivo-like tissues called organoids. Organoids represent multiple histological and functional aspects of real organs and offer unprecedented perspectives for modelling tissue development, regeneration, and disease in vitro. However, relying so far almost exclusively on spontaneous self-organisation of stem cells, organoids develop uncontrollably into small structures of highly variable size and architecture. Moreover, the closed, cystic architecture of most epithelial organoids limits their lifespan and makes experimental manipulation difficult. In this thesis, three innovative engineering technologies were developed that offer the possibility of steering in vitro stem cell patterning and organoid formation into more controllable and physiologically relevant miniature tissues.	The aim of the first project was to study how predefined geometric constraints, as they exist in vivo, affect organoid development. This required the development of a novel fabrication process of the topographically micro-patterned hydrogel surfaces. This approach allowed the generation of large arrays of the identical organoids, having pre-defined shape and size to study cellular mechanisms involved in the proper, stereotypical cell type pattering of intestinal organoids.		The second project focused on replicating tissue dynamics and aspects of organ physiology by developing a novel three-dimensional organ-on-chip approach. Using stem cells derived from patient biopsies, this technology enables to production of miniature versions of patientâs organs that can be used in personalized diagnostics and medical treatment assays.	Bioprinting has long been considered as one of the most promising technologies for fabricating organs in vitro. However, despite encouraging advances made in recent years, the degree of multicellular spatial complexity and function of organoids remains unmatched by any existing bioprinting technology. Therefore, the third project was aimed to develop a new bioprinting strategy that preserves local stem cell self-organization potential and extends organoids growth to the macroscopic scale.	Overall, this thesis introduces several cutting-edge technologies that offer the possibility to control in vitro organoid development and should therefore become efficient research tools to facilitate the translation of organoid technology towards pharmaceutical and clinical applications. Hydrogel micro-pattering is an efficient technology that can be widely used to explore the mechanisms by which tissue geometry can regulate morphogenesis of different organs and can be readily applied for high-throughput screening in pharmacological assays. The microscope-based bioprinter can be set-up in any laboratory to guide stem cell self-organization and tissue morphogenesis from millimetre to centimetre scales. The microfluidic organoid-on-chip concept should enable the creation of various miniature organs with complex three-dimensional spatial organisation and multicellular complexity for basic research and drug discovery.

EPFL2021

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

Engineering next generation organoids through guided stem cell self-organisation

Mikhail Nikolaev

One of the long-standing goals in the field of tissue engineering is the fabrication of de novo tissues or even organs to provide better tissue models for basic research and drug discovery, and to alleviate a shortage of donor organs in the future. Research in recent decades to understand tissue biology has led to the discovery of stem cell niches and the development of innovative protocols for the generation of three-dimensional in vivo-like tissues called organoids. Organoids represent multiple histological and functional aspects of real organs and offer unprecedented perspectives for modelling tissue development, regeneration, and disease in vitro. However, relying so far almost exclusively on spontaneous self-organisation of stem cells, organoids develop uncontrollably into small structures of highly variable size and architecture. Moreover, the closed, cystic architecture of most epithelial organoids limits their lifespan and makes experimental manipulation difficult. In this thesis, three innovative engineering technologies were developed that offer the possibility of steering in vitro stem cell patterning and organoid formation into more controllable and physiologically relevant miniature tissues.	The aim of the first project was to study how predefined geometric constraints, as they exist in vivo, affect organoid development. This required the development of a novel fabrication process of the topographically micro-patterned hydrogel surfaces. This approach allowed the generation of large arrays of the identical organoids, having pre-defined shape and size to study cellular mechanisms involved in the proper, stereotypical cell type pattering of intestinal organoids.		The second project focused on replicating tissue dynamics and aspects of organ physiology by developing a novel three-dimensional organ-on-chip approach. Using stem cells derived from patient biopsies, this technology enables to production of miniature versions of patientâs organs that can be used in personalized diagnostics and medical treatment assays.	Bioprinting has long been considered as one of the most promising technologies for fabricating organs in vitro. However, despite encouraging advances made in recent years, the degree of multicellular spatial complexity and function of organoids remains unmatched by any existing bioprinting technology. Therefore, the third project was aimed to develop a new bioprinting strategy that preserves local stem cell self-organization potential and extends organoids growth to the macroscopic scale.	Overall, this thesis introduces several cutting-edge technologies that offer the possibility to control in vitro organoid development and should therefore become efficient research tools to facilitate the translation of organoid technology towards pharmaceutical and clinical applications. Hydrogel micro-pattering is an efficient technology that can be widely used to explore the mechanisms by which tissue geometry can regulate morphogenesis of different organs and can be readily applied for high-throughput screening in pharmacological assays. The microscope-based bioprinter can be set-up in any laboratory to guide stem cell self-organization and tissue morphogenesis from millimetre to centimetre scales. The microfluidic organoid-on-chip concept should enable the creation of various miniature organs with complex three-dimensional spatial organisation and multicellular complexity for basic research and drug discovery.

EPFL2021