1b:I[76749,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 1c:I[3486,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 1d:I[41892,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 1e:I[17707,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 1f:I[66528,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 20:I[63176,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 21:I[87099,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 22:I[26200,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"Group"] 23:I[23365,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 24:T4dc,Gain-of-function mutations in the protein-tyrosine phosphatase SHP2 are the most frequently occurring mutations in sporadic juvenile myelomonocytic leukemia (JMML) and JMML-like myeloproliferative neoplasm (MPN) associated with Noonan syndrome (NS). Hematopoietic stem and progenitor cells (HSPCs) are the disease propagating cells of JMML. Here, we explored transcriptomes of HSPCs with SHP2 mutations derived from JMML patients and a novel NS zebrafish model. In addition to major NS traits, CRISPR/Cas9 knock-in Shp2^D61G mutant zebrafish recapitulated a JMML-like MPN phenotype, including myeloid lineage hyperproliferation, ex vivo growth of myeloid colonies, and in vivo transplantability of HSPCs. Single-cell mRNA sequencing of HSPCs from Shp2^D61G zebrafish embryos and bulk sequencing of HSPCs from JMML patients revealed an overlapping inflammatory gene expression pattern. Strikingly, an anti-inflammatory agent rescued JMML-like MPN in Shp2^D61G zebrafish embryos. Our results indicate that a common inflammatory response was triggered in the HSPCs from sporadic JMML patients and syndromic NS zebrafis

Florian Piques

Publications