generation-of-human-blood-vessel-organoids-from-pluripotent-stem-cells

Generation of Human Blood Vessel Organoids from Pluripotent Stem Cells

An organoid is defined as an engineered multicellular in vitro tissue that mimics its corresponding in vivo organ such that it can be used to study ...

University of British Columbia

Recent studies have unveiled unique functions of the bone marrow adipose tissue (BMAT), which represent over 10% of the total adipose tissue mass in healthy adults. Increasing evidence is emerging as to how BMAT deposition and osteoporosis are linked under normal and pathophysiological conditions, which is opening up novel treatment avenues. However, the means by which bone marrow adipocytes (BMAs) regulate bone remodeling and their involvement in osteoporosis remained unknown. A study in this issue of EMBO Reports (Hu et al, 2021) and a study in Journal of Clinical Investigation (Yu et al, 2021) reports independently that BMA-derived RANKL regulates osteoclastogenesis and bone remodeling, indicating that excessive RANKL generated by BMAs is an underlying cause for osteoporosis.

A critical relationship between bone and fat: the role of bone marrow adipose-derived RANKL in bone metabolism.

The mechanism by which morphogenetic signals engage the regulatory networks responsible for early embryonic tissue patterning is incompletely understood. Here, we developed a minimal gene regulatory network (GRN) model of human pluripotent stem cell (hPSC) lineage commitment and embedded it into "cellular" agents that respond to a dynamic morphogenetic signaling microenvironment. Simulations demonstrated that GRN wiring had significant non-intuitive effects on tissue pattern order, composition, and dynamics. Experimental perturbation of GRN connectivities supported model predictions and demonstrated the role of OCT4 as a master regulator of peri-gastrulation fates. Our so-called GARMEN strategy provides a multiscale computational platform to understand how single-cell-based regulatory interactions scale to tissue domains. This foundation provides new opportunities to simulate the impact of network motifs on normal and aberrant tissue development.

Nicolas Werschler

School of Biomedical Engineering,
Life Sciences Institute

University of British Columbia

Generation of Human Blood Vessel Organoids from Pluripotent Stem Cells

Nicolas Werschler

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University of British Columbia

Generation of Human Blood Vessel Organoids from Pluripotent Stem Cells

School of Biomedical Engineering,
Life Sciences Institute