Luke Kullback
Research Mentor(s): Idse Heemskerk
Mentor Department: cell and developmental biology
Authors: Luke Kullback, Bohan Chen, Idse Heemskerk
Session: Session 3 (11:00am – 11:50am)
Presentation Type: Poster 35
Abstract
Pluripotent stem cell (PSC) derived primitive gut endoderm cells hold great promise for regenerative medicine repair of thyroid, lungs, pancreas, liver, and intestines diseases as well as in vitro diseases modeling and drug screening. To differentiate into specific types of primitive gut endoderm cells, PSCs first need to go through two differentiation stages in vitro, which mimic the developmental stages of ‘primitive streak’ differentiation and ‘mesendoderm’ segregations, to be specified into an intermediate cell state called definitive endoderm (DE). DE can then be patterned toward anterior-posterior primitive gut endoderm cells, including foregut, midgut, and hindgut progenitors, for the downstream applications mentioned above. However, with the current knowledge, typical DE and primitive gut endoderm differentiation protocols yield highly variable results that contain unintentional and heterogeneous cell lineages, most notably mesodermal populations. Despite BMP & WNT signalings have been known to be critical for mesoderm fates, while Nodal & FGF signalings favor endoderm fates, the specific mechanisms for the interactions of those signalings underlying the cell heterogeneities remain poorly understood. Notably, despite the endo- and mesodermal heterogeneity, in many cases, the mixed mesodermal lineages are indispensable for supporting the growth of certain endodermal populations, for example, during the process of human primitive gut organoid induction. Therefore, obtaining the control of the mesodermal lineage emergence and understanding the temporal signaling dynamics of DE induction, patterning, and the role of the mixed mesodermal populations are essential for comprehending the fundamental developmental processes and robust application of the primitive gut endoderm cells. In this study, we will explore the independent and combinatory effects of BMP and FGF signalings. We hypothesize that there is a negative feedback loop between BMP and FGF that controls the switch to endoderm over mesoderm and anterior versus posterior.
