Abstract
Generation of kidney organoids from pluripotent stem cells (PSCs) is regarded as a potentially powerful way to study kidney development, disease, and regeneration. Direct differentiation of PSCs towards renal lineages is well studied; however, most of the studies relate to generation of nephron progenitor population from PSCs. Until now, differentiation of PSCs into ureteric bud (UB) progenitor cells has had limited success. Here, we describe a simple, efficient, and reproducible protocol to direct differentiation of mouse embryonic stem cells (mESCs) into UB progenitor cells. The mESC-derived UB cells were able to induce nephrogenesis when co-cultured with primary metanephric mesenchyme (pMM). In generated kidney organoids, the embryonic pMM developed nephron structures, and the mESC-derived UB cells formed numerous collecting ducts connected with the nephron tubules. Altogether, our study established an uncomplicated and reproducible platform to generate ureteric bud progenitors from mouse embryonic stem cells.
Highlights
Pluripotent stem cells (PSCs) possess great potential of differentiating into multiple cell types that are widely used for studies in developmental biology and regenerative medicine [1]
Direct Differentiation of mouse embryonic stem cells (mESCs) into UB Progenitor Cells. Both the nephron and ureteric bud progenitor cells are derived from the intermediate mesoderm (IM)
We treated the mESCs with FGF2 and activin A to differentiate mESCs into epiblast in monolayer culture (Supplementary Figure S1A)
Summary
Pluripotent stem cells (PSCs) possess great potential of differentiating into multiple cell types that are widely used for studies in developmental biology and regenerative medicine [1]. We and several other groups reported induction of nephron progenitors, which have the potential to develop into epithelial nephron-like structures [2,3,4,8,11,12,13,14,15,16,17,18]. A newly published study has shown generation of UB structures from PSCs, which possessed UB-like branching morphogenesis when aggregated with the primary metanephric mesenchyme (pMM) to form chimeric kidney organoids [8]. The protocol is technically complex, which limits its application Analysis of these reports suggests that we still need further studies to develop simple, reproducible, and stable protocols for UB progenitor generation
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