Transcriptomics

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CALR mutation-induced transcriptional changes in cord blood-derived hematopoietic stem and progenitor cells


ABSTRACT: Recurrent mutations in calreticulin (CALR) are present in 70-80% of JAK2 unmutated myeloproliferative neoplasms (MPN). Current models of CALR mutant MPNs are mainly based on cancer cell lines with ectopic overexpression or transgenic mouse models with a lack of data for primary human hematopoietic stem and progenitor cells (HSPCs) with endogenous CALR expression. Thus, we developed a CRISPR/Cas9 and AAV6-mediated knock-in approach to introduce the two most common CALR mutations (52 bp deletion, DEL; 5 bp insertion, INS) at the endogenous gene locus in human cord blood-derived HSPCs. We used these cells to investigate transcriptional changes induced upon CALR mutation acquisition in HSPCs in a prospective manner by performing RNA-sequencing 4 days after CRISPR-mediated knock-in.

ORGANISM(S): Homo sapiens

PROVIDER: GSE195705 | GEO | 2023/01/09

REPOSITORIES: GEO

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