{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T16:46:48Z","timestamp":1776530808475,"version":"3.51.2"},"posted":{"date-parts":[[2026,4,15]]},"group-title":"Genomics","reference-count":63,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["KL2 TR002015"],"award-info":[{"award-number":["KL2 TR002015"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hyundai Hope on Wheels Scholar Grant"},{"name":"Four Diamonds Fund of the Pennsylvania State University College of Medicine"},{"name":"John Wawrynovic Leukemia Research Scholar Endowment"},{"name":"St. Baldrick\u2019s Foundation"},{"name":"Team Connor and Rally Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Casein Kinase 2 (CK2) is a constitutively active kinase regulating proliferation and immune signaling and is frequently dysregulated in cancer, including acute myeloid leukemia (AML), making it a therapeutic target. CK2 comprises two catalytic subunits, CK2\u03b1 or CK2\u03b1\u2019, with two regulatory \u03b2 subunits. The role of CK2\u03b1, the predominant catalytic subunit and principal mediator of CK2 kinase activity in hematopoietic cells, in steady-state hematopoiesis remains undefined. To define how CK2\u03b1 shapes hematopoietic cells, we used bone marrow and spleen tissue samples of wild type control and conditional knock out (KO) of CK2\u03b1 (\n                  <jats:italic>Csnk2a1<\/jats:italic>\n                  ) in the hematopoietic compartment of transgenic mice. Using single-cell RNA sequencing, we profiled the transcriptomic changes associated with CK2\u03b1 loss. Although HSC abundance was comparable between the control and CK2\u03b1-deficient samples, HSCs experienced the largest transcriptional response to CK2\u03b1 loss among all cell types. CK2\u03b1-deficient HSCs displayed transcriptional remodeling for inflammatory and immune-associated programs, interferon signaling, and antigen presentation. Expression of inflammatory genes such as\n                  <jats:italic>S100a8<\/jats:italic>\n                  and\n                  <jats:italic>S100a9<\/jats:italic>\n                  , changed in opposite directions in bone marrow and spleen HSCs, demonstrating the transcriptional consequences of CK2\u03b1 loss shaped by tissue context. Using a network-based approach, we identified immune-associated transcription factors\n                  <jats:italic>Nfkb1, Rfx5, Hes1<\/jats:italic>\n                  , and AP-1 family members as regulatory hubs driving these inflammatory transcriptional states in CK2\u03b1-deficient HSCs. Cell-cell communication profiling revealed multiple gains and losses in ligand-receptor communication between the HSCs and their immune microenvironment in KO. Our findings identify CK2\u03b1 as a regulator of immune transcriptional programs in HSCs and suggest that disruption of CK2 signaling influences stem cell behavior and immune activation in contexts relevant to hematologic malignancies and CK2-targeted cancer therapies.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Statement of significance<\/jats:title>\n                  <jats:p>This study reveals that inhibiting the protein CK2\u03b1 forces blood stem cells into a stressed, immune-primed state. These tissue-specific findings highlight potential side effects for cancer therapies targeting this essential regulatory kinase.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.10.717787","type":"posted-content","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T11:00:39Z","timestamp":1776250839000},"source":"Crossref","is-referenced-by-count":0,"title":["Lineage-specific CK2\u03b1 deletion reshapes the transcriptome of hematopoietic stem cells toward an immune-primed state"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4299-5903","authenticated-orcid":false,"given":"Hannah","family":"Valensi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajesh","family":"Rajaiah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marudhu","family":"Shanmugam","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniyal","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Upendar","family":"Golla","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Mercer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anush","family":"Karampuri","sequence":"additional","affiliation":[{"name":"Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sinisa","family":"Dovat","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA"},{"name":"Department of Molecular and Precision Medicine, Pennsylvania State University College of Medicine, Hershey, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandrika","family":"Behura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasin","family":"Uzun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA"},{"name":"Department of Molecular and Precision Medicine, Pennsylvania State University College of Medicine, Hershey, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041809350485000_2026.04.10.717787v1.1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27625"},{"key":"2026041809350485000_2026.04.10.717787v1.2","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/s41408-024-01140-5","article-title":"Therapy-related AML: long-term outcome in a large cohort of AML-patients with intensive and non-intensive therapy","volume":"14","year":"2024","journal-title":"Blood Cancer J"},{"key":"2026041809350485000_2026.04.10.717787v1.3","first-page":"177","volume-title":"Semin Hematol","volume":"62","year":"2025"},{"key":"2026041809350485000_2026.04.10.717787v1.4","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1182\/asheducation-2016.1.348","article-title":"Mutations in AML: prognostic and therapeutic implications. 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