hPSC-derived Sacral Neural Crest Enables Rescue in a Severe Model of Hirschsprung’s Disease [ATAC-seq]

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UID: 11024

Author(s): Fan, Yujie* * MSK affiliated

Description: Summary from GEO:

"The enteric nervous system (ENS) is derived from both the vagal and sacral component of the neural crest (NC). Here, we present the derivation of sacral ENS precursors from human PSCs via timed exposure to FGF, WNT and to GDF11 to enable posterior patterning and transition from posterior trunk to sacral NC identity respectively. Using a SOX2::H2B-tdTomato/ T::H2B-GFP dual reporter hPSC line, we demonstrate that both trunk and sacral NC emerge from a double-positive neuro-mesodermal progenitor (NMP). Vagal and sacral NC precursors yield distinct neuronal subtypes and migratory behaviors in vitro and in vivo. Remarkably, xenografting of both vagal and sacral NC lineages is required to rescue a mouse model of total aganglionosis, suggesting novel opportunities in the treatment of severe forms of Hirschsprung’s disease."

Overall design from GEO:

"RNA seq data and ATAC seq data of a series of samples collected at different time points, comparing cells treated with or without GDF11."

Subject of Study

Subject(s)

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