The IP Stem Cell Initiative

About

The Stem Cell Concept – Constructing, Deconstructing and Reconstructing Tissues for organismal health

Human biology and molecular medicine are rapidly becoming data-rich fields that are fueled in part by large-scale longitudinal studies of patients involving imaging and omics. However, without the appropriate conceptual framework, gaining functional insights of medical relevance from this data is a major challenge.

Human physiology and health rely on quintessential properties of living tissues and organisms, namely their capacity to build reproducibly functional structures/organs (biological precision), to cope with perturbations (robustness and adaptability), and to develop new functionalities (plasticity). These emerging properties can be encapsulated at all scales (from molecules to cells, tissues, organs, and organisms) and integrate the life-history of the cells/organisms (through cellular memory and/or priming) and contextual information (neighboring cells/tissue/environment) (Figure 1). Therefore, multiscale studies of stem cells and cell ensembles, combined with computational approaches, can provide the context needed to understand human physiology in health and disease.

Work covered by the Stem Cell initiative addresses the mechanisms by which stem and progenitor cells choose and adjust their properties, position and fate at the interface of individual cellular programs and the tissue or organismal functional needs. At the molecular level, we study gene regulatory processes with an emphasis on the concepts of memory of past states and priming of new identities. At the cellular level, we aim to understand how cells integrate and process information to execute fate decisions such as proliferation, differentiation, or apoptosis. At the multi-cellular level, we focus on how critical cell-cell interactions and signaling, together with mechanical properties, result in the shape and function of tissues and organs. Eventually, we integrate long range communication between organs to understand the physiology and the adaption of the organism to fluctuating environment and stress.

By using cutting-edge technologies such as single cell multi-omics and imaging (from super resolution to whole mount 4D long-term live imaging), we aim to interpret these processes at the sub-cellular, cellular and supra-cellular levels and ultimately perform predictive biology in normal and pathological development and physiology. This will provide a powerful and rational approach to gain a mechanistic understanding and predictive power of human physiological systems so that patient care can be improved and new treatments for diseases developed.

Generating fundamental knowledge

Developing technologies exploiting Stem Cells or associated mechanisms

iPSCs
organoids
embryoids
organ on chip…

Building bridges towards key medical applications

Congenital and developmental defects, reproductive medicine
Cancer
Ageing
Regenerative medicine
Long-term effects of organismal challenges (infection, nutrition, stress…)

**An integrated and multiscale view of physiology and disease**

On Mon 11/18, we held a mini symposium on the novel perspectives in human embryo research and Stem cell day. Lively discussions thanks to our prominent speakers and participants!

On November 18th, the Institut Pasteur held the Mini-Symposium: “The Human Embryo: Novel Perspectives in Research and Disease Mechanisms” associated with the annual meeting of the Institut Pasteur Stem Cell Initiative.

The morning symposium was covering the current status of research on the human embryo and human embryo models, including current challenges and technical innovations to study human development from fertilization to embryonic and fetal development. Leading international experts provided exciting insights on the creation on novel 3D human embryos atlases and biobanks, novel stem-cell based model to study early human development, fertility and sex determination to the ethical considerations on human embryo and stem cell research.

The afternoon was dedicated to the annual meeting of the IP Stem Cell Initiative. Six presentations were covering the breadth of research projects using stem cells on campus, from the development of novel stem cell based embryo models (Giada Mura, DSCB), using organ-on-chip to study the impact of microenvironment on infection (Remigiuiz Walocha, DSCB), the impact of early life stress on adult stem cell behaviour (Fabian Guendel, Immuno dept.), the role of blood factors in neural stem cell ageing (Lida Katpsimpardi, Neuro dept. / Institut Necker) or the role of large scale genome reorganization for stem cell totipotency regulation (Jack-Christophe Cossec, BCI). These presentations were followed by a brief historical overview on the study of small RNAs in C. Elegans by Germano Cecere (DSCB) to celebrate the recent Nobel Prize for the discovery of microRNAs.

The presentations were followed by a poster session at the François Jacob Atrium, providing a convivial and scientific moment to discuss ongoing projects and connect researchers across departments.