BMP Signaling Promotes Immune Cell Differentiation in Human Intestinal Organoids

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

Abstract

Project Abstract Human pluripotent stem cell (hPSC) derived human intestinal organoids (HIOs) are a powerful model since they possess many lineages, including epithelium, smooth muscle, neurons, and endothelial cells; however, HIOs lack immune populations, which are key to studying the development and maturation of the intestine. Since early HIOs possess mesoderm, I tested the hypothesis that this population may respond to cues, such as BMP signaling, that induce immune cell differentiation. Preliminary data supports a role for BMP signaling as an inductive cue for CD45+ immune cells within small intestinal HIOs. This proposal will test the hypothesis that early HIOs retain plasticity soon after intestinal patterning and have mesenchyme-specific responses to BMP signaling, which leads to differentiation of the mesenchyme into hemogenic endothelium that will further differentiate into functional immune lineages. I aim to interrogate the mechanism by which BMP4 induces immune-like cells, through a hemogenic endothelium intermediate, in HIOs, including the cell intermediates required for immune cell differentiation. Secondly, I aim to investigate the lineages of immune cells present and functionally evaluate the immune-like cells in the HIOs.