LGR5 and obesity due to melanocortin 4 receptor deficiency: The possibility that obesity impacts the proliferative potential of human ISCs is not easy to test; however, there are already experimental methodologies that suggest the feasibility of indirect research approaches: (1) actively cycling ISCs (CBCs) can be identified based upon several markers, including the expression of LGR5 59,60, and (2) isolation of human ISCs from whole tissue or biopsies has been described, and such cells have been assessed in three-dimensional organoids (“colonoids”) 61.