TY - JOUR
T1 - Expansion and Maturation of Innate Lymphoid Cell Precursors Using Human iPSC-Derived Intestinal Organoids
AU - Kromann, Emma Højmose
AU - Jowett, Geraldine M
AU - Neves, Joana F
N1 - © 2024. Springer Science+Business Media, LLC.
PY - 2024/8/31
Y1 - 2024/8/31
N2 - Innate lymphoid cells (ILC) are enriched at mucosal barrier sites where they play critical roles in development and disease. Mucosal organoids offer a robust platform for the simultaneous differentiation and expansion of all subsets of mature ILC from a shared peripheral blood precursor. Critically, organoid identity drives tissue-specific imprinting of the culture-derived mature innate lymphoid cells, allowing for the study of bidirectional interactions between, e.g., intestinal organoids and intestine-specific ratios and populations of ILC. This protocol reduces the need for feeder cell lines and complex cytokine cocktails used to mature and maintain ILC, instead relying on a native niche of protein signals provided by mucosal epithelial cells. This protocol details the generation of human intestinal organoids (HIO) from human-induced pluripotent stem cells (hiPSC), and the subsequent establishment of co-cultures between HIO and ILC precursors for expansion and maturation. This approach has extensive applications for mechanistic studies of fundamental biological processes and as a potential GMP-compatible source of ILC for future cell therapies.
AB - Innate lymphoid cells (ILC) are enriched at mucosal barrier sites where they play critical roles in development and disease. Mucosal organoids offer a robust platform for the simultaneous differentiation and expansion of all subsets of mature ILC from a shared peripheral blood precursor. Critically, organoid identity drives tissue-specific imprinting of the culture-derived mature innate lymphoid cells, allowing for the study of bidirectional interactions between, e.g., intestinal organoids and intestine-specific ratios and populations of ILC. This protocol reduces the need for feeder cell lines and complex cytokine cocktails used to mature and maintain ILC, instead relying on a native niche of protein signals provided by mucosal epithelial cells. This protocol details the generation of human intestinal organoids (HIO) from human-induced pluripotent stem cells (hiPSC), and the subsequent establishment of co-cultures between HIO and ILC precursors for expansion and maturation. This approach has extensive applications for mechanistic studies of fundamental biological processes and as a potential GMP-compatible source of ILC for future cell therapies.
U2 - 10.1007/7651_2024_568
DO - 10.1007/7651_2024_568
M3 - Article
C2 - 39214947
SN - 1064-3745
JO - Methods in molecular biology (Clifton, N.J.)
JF - Methods in molecular biology (Clifton, N.J.)
ER -