---
title: "JDP2 depletion disrupts cell-cycle homeostasis in colorectal epithelial cells — single-cell profil"
id: "biorxiv-11-single-cell-profiling-reveals-disruption-of-cell-cycle-homeostasis-following"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-11-single-cell-profiling-reveals-disruption-of-cell-cycle-homeostasis-following"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.14.751340v1?rss=1"
published_at: "2026-09-19T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# JDP2 depletion disrupts cell-cycle homeostasis in colorectal epithelial cells — single-cell profil
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-11-single-cell-profiling-reveals-disruption-of-cell-cycle-homeostasis-following
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.14.751340v1?rss=1)
- **Published At:** 2026-09-19T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study examines the role of **JDP2** (Jun dimerization protein 2) in intestinal epithelial cells (IECs) and its association with cell-cycle regulation in colorectal contexts using functional assays and single-cell RNA sequencing. - Clinical data from patients in the source showed that higher **JDP2** expression correlated with significantly worse survival compared with lower expression; no further clinical cohort details were reported in the source. - In vitro functional assays after JDP2 depletion showed increased EdU incorporation during S phase and higher PHH3 abundance, indicating raised proliferative and mitotic activity among colorectal epithelial cells. - Single-cell transcriptomic profiling revealed reprogramming of **cell-cycle** transcriptional states after JDP2 knockdown, with differential expression of genes involved in cyclins, cyclin-dependent kinases, chromosome segregation, and mitotic progression. - Cells with lower residual **JDP2** expression exhibited increased representation of the G2/M phase and shifted toward later states along a G1 → S → G2/M-associated transcriptional trajectory. - Quantitatively, low-JDP2 cells occupied late transcriptional states more frequently than high-JDP2 cells (33.6% vs 24.0%; paired P = 0.048), as reported in the source. - Among JDP2-siRNA-treated cells, residual JDP2-expressing cells displayed heterogeneous associations of JDP2 with programs related to cell-cycle, survival, apoptosis, and stress response, consistent with context-dependent transcriptional roles. - The authors conclude that **JDP2** is an important regulator of intestinal epithelial **cell-cycle homeostasis** and that its depletion perturbs the balance of proliferative cell states; mechanistic and in vivo details beyond those reported were not provided in the source.
## Clinical Analysis & Structured Key Points
Single-cell profiling reveals disruption of cell-cycle homeostasis following JDP2 depletion in colorectal epithelial cells | bioRxiv Skip to main content New Results Single-cell profiling reveals disruption of cell-cycle homeostasis following JDP2 depletion in colorectal epithelial cells Violet Newhart , Angela Gao , Anna Edens , Madison Flory , Paloma Bravo , Ashfaqul Alam doi: https://doi.org/10.64898/2026.09.14.751340 Violet Newhart University of Kentucky Find this author on Google Scholar Find this author on PubMed Search for this author on this site Angela Gao University of Kentucky Find this author on Google Scholar Find this author on PubMed Search for this author on this site Anna Edens University of Kentucky Find this author on Google Scholar Find this author on PubMed Search for this author on this site Madison Flory University of Kentucky Find this author on Google Scholar Find this author on PubMed Search for this author on this site Paloma Bravo University of Kentucky Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ashfaqul Alam University of Kentucky Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: maal324{at}uky.edu Abstract Info/History Metrics Preview PDF Abstract Intestinal epithelial cells (IECs) undergo rapid and continuous renewal to maintain gut epithelial homeostasis and barrier integrity at the interface with luminal microbiota, dietary antigens, and enteric pathogens. IEC proliferation is tightly regulated by a complex machinery of cell cycle regulators and effectors, and genetic or transcriptional dysregulation of cell-cycle regulatory pathways is a hallmark of colorectal cancer development and progression. Previously, JDP2 (Jun dimerization protein 2) has been shown to be involved in cell cycle control and is associated with an array of cancers. JDP2 functions as a transcription factor or epigenetic regulator depending on cellular context, disease, and cancer types. However, the role of JDP2 in CRC, cell cycle homeostasis of colon cancer cells, and their fate remains poorly defined. In this study, we found that patients with higher JDP2 expression have significantly worse survival than patients with lower JDP2 expression. Our functional assays showed that JDP2 depletion increased EdU incorporation during S phase and PHH3 abundance, which is consistent with increased proliferative and mitotic activity. Our single-cell RNA sequencing and transcriptomic profiling further revealed reprogramming of cell-cycle-associated transcriptional states following JDP2 depletion. Differential-expression and pathway analysis identified changes in mitotic and cell-cycle regulatory genes, including programs involving cyclins, cyclin-dependent kinases, chromosome segregation, and mitotic progression. We also found that lower residual JDP2 expression was associated with escalated G2/M representation and a change toward later states along a G1 - S - G2/M-associated transcriptional trajectory. Furthermore, low-JDP2 cells showed significantly greater late-state occupancy than High-JDP2 cells (33.6% versus 24.0%; paired P=0.048). Among the JDP2-siRNA-treated cells, analysis of residual JDP2-expressing cells also revealed heterogeneous associations of JDP2 with cell-cycle, survival, apoptotic, and stress-response programs, consistent with JDP2's context-dependent transcriptional functions. Together, these data identify JDP2 as an important component of intestinal epithelial cell-cycle homeostasis and transcriptional landscape and suggest that JDP2 depletion perturbs the balance of proliferative cell states. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared National Institute of General Medical Sciences, https://ror.org/04q48ey07 , 5P20GM130456-07 (A.A.; Alam Project ID 9180) NIDDK , R56DK136728 NIDDK , K01DK114391 ACS IRG Elsa U. Pardee Foundation Grant Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Back to top Previous Next Posted September 19, 2026. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. 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Share Single-cell profiling reveals disruption of cell-cycle homeostasis following JDP2 depletion in colorectal epithelial cells Violet Newhart , Angela Gao , Anna Edens , Madison Flory , Paloma Bravo , Ashfaqul Alam bioRxiv 2026.09.14.751340; doi: https://doi.org/10.64898/2026.09.14.751340 Share This Article: Copy Citation Tools Single-cell profiling reveals disruption of cell-cycle homeostasis following JDP2 depletion in colorectal epithelial cells Violet Newhart , Angela Gao , Anna Edens , Madison Flory , Paloma Bravo , Ashfaqul Alam bioRxiv 2026.09.14.751340; doi: https://doi.org/10.64898/2026.09.14.751340 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8013) Biochemistry (18737) Bioengineering (14888) Bioinformatics (44415) Biophysics (22597) Cancer Biology (19722) Cell Biology (26899) Clinical Trials (138) Developmental Biology (13964) Ecology (21005) Epidemiology (2067) Evolutionary Biology (25454) Genetics (16165) Genomics (23505) Immunology (18703) Microbiology (42483) Molecular Biology (18058) Neuroscience (93440) Paleontology (700) Pathology (2977) Pharmacology and Toxicology (5094) Physiology (8114) Plant Biology (15999) Scientific Communication and Education (2095) Synthetic Biology (4560) Systems Biology (10235) Zoology (2391)
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