{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:17Z","timestamp":1792790357307,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,17]]},"group-title":"Molecular Biology","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIAID","award":["R01 AI162879"],"award-info":[{"award-number":["R01 AI162879"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIAID","award":["R01 AI155540"],"award-info":[{"award-number":["R01 AI155540"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,17]]},"abstract":"<jats:p>Yin Yang 1 (YY1) is a multifunctional transcription factor involved in chromatin organization and gene regulation. While the mechanisms by which YY1 controls B cell lineage development have been explored at the transcriptional level, little is known at the post-transcriptional level. To address this, we performed integrated analyses combining bulk transcriptomics, miRNA profiling, and single-cell transcriptomics to identify YY1-dependent regulatory networks at the pro-B cell stage. YY1 knockout (KO) in pro-B cells leads to reduced B-lineage commitment and activation of genes associated with alternative hematopoietic fates. Our integrative analyses suggest that these changes are organized in part through coordinated miRNA-mRNA regulatory networks. In wild-type (WT) pro-B cells, miRNAs such as miR-10a-5p, miR-674-5p, and miR-21a-5p maintain B cell identity by suppressing RNAs linked to other lineages. In contrast, in YY1 KO pro-B cells increased expression of miRNAs including miR-15b-5p, miR-342-5p, and miR-34a-5p target pathways required for B cell development, proliferation, and survival thus reducing B lineage identity. Together, these findings suggest that YY1 preserves B cell identity through coordinated regulation of transcriptional and post-transcriptional programs, with YY1-dependent miRNA networks contributing to the maintenance of B cell-associated gene expression and restriction of alternative lineage programs. Among these, miR-15b-5p emerged as a central regulator predicted to regulate Bcl6b and E2f family transcription factors that control proliferative and transcriptional programs critical for early B cell development. At single-cell resolution, YY1 KO pro-B cells grown on OP9-DL4 feeders that provide Notch signaling displayed marked transcriptional heterogeneity and loss of pro-B lineage commitment. Pseudotime analysis revealed a branched developmental landscape, with cells diverging toward monocyte, macrophage, and dendritic cell fates rather than a consistent B cell differentiation trajectory. Collectively, these findings establish YY1 as a central regulator of lineage commitment integrating transcriptional and miRNA-mediated post-transcriptional mechanisms to regulate B cell identity.<\/jats:p>","DOI":"10.64898\/2026.09.15.751727","type":"posted-content","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:05:13Z","timestamp":1789664713000},"source":"Crossref","is-referenced-by-count":0,"title":["miRNA-mediated regulation of lineage plasticity in YY1 knockout pro-B cells"],"prefix":"10.64898","author":[{"given":"Nasreen","family":"Bano","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania 3800 Spruce St., Philadelphia, PA 19038"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Naiyer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania 3800 Spruce St., Philadelphia, PA 19038"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulagna","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania 3800 Spruce St., Philadelphia, PA 19038"},{"name":"Jefferson University, 1020 Walnut St. Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchita","family":"Hodewadekar","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania 3800 Spruce St., Philadelphia, PA 19038"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Atchison","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania 3800 Spruce St., Philadelphia, PA 19038"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091914500405000_2026.09.15.751727v1.1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.10.7237"},{"key":"2026091914500405000_2026.09.15.751727v1.2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.351734.124"},{"key":"2026091914500405000_2026.09.15.751727v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209080"},{"key":"2026091914500405000_2026.09.15.751727v1.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603564103"},{"key":"2026091914500405000_2026.09.15.751727v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.10.015"},{"issue":"1","key":"2026091914500405000_2026.09.15.751727v1.6","doi-asserted-by":"crossref","first-page":"21781","DOI":"10.1038\/s41598-020-78544-3","article-title":"YY1 directly interacts with myocardin to repress the triad myocardin\/SRF\/CArG box-mediated smooth muscle gene transcription during smooth muscle phenotypic modulation","volume":"10","year":"2020","journal-title":"Sci Rep"},{"key":"2026091914500405000_2026.09.15.751727v1.7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402525200"},{"key":"2026091914500405000_2026.09.15.751727v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.008"},{"issue":"10","key":"2026091914500405000_2026.09.15.751727v1.9","doi-asserted-by":"crossref","first-page":"101583","DOI":"10.1016\/j.isci.2020.101583","article-title":"Erythropoietin Regulates Transcription and YY1 Dynamics in a Pre-established Chromatin Architecture","volume":"23","year":"2020","journal-title":"iScience"},{"key":"2026091914500405000_2026.09.15.751727v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52375-6"},{"key":"2026091914500405000_2026.09.15.751727v1.11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00045"},{"key":"2026091914500405000_2026.09.15.751727v1.12","doi-asserted-by":"publisher","DOI":"10.1101\/gr.215160.116"},{"key":"2026091914500405000_2026.09.15.751727v1.13","doi-asserted-by":"crossref","first-page":"105249","DOI":"10.1016\/j.exphem.2025.105249","article-title":"Three-dimensional genome reorganization in hematopoietic stem cells","volume":"152","year":"2025","journal-title":"Exp Hematol"},{"key":"2026091914500405000_2026.09.15.751727v1.14","unstructured":"Althwaiqeb, S.A. , A.O. 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