---
title: "Monocyte reprogramming after autologous stem cell transplantation in juvenile systemic sclerosis:"
id: "biorxiv-4-longitudinal-single-cell-modeling-reveals-monocyte-reprogramming-in-juvenile"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-4-longitudinal-single-cell-modeling-reveals-monocyte-reprogramming-in-juvenile"
content_type: "clinical_feed_article"
specialty: "Rheumatology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.08.21.738279v1?rss=1"
published_at: "2026-08-26T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Monocyte reprogramming after autologous stem cell transplantation in juvenile systemic sclerosis:
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-4-longitudinal-single-cell-modeling-reveals-monocyte-reprogramming-in-juvenile
- **Specialty:** [Rheumatology](https://medichelpline.com/clinical-feed/rheumatology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.08.21.738279v1?rss=1)
- **Published At:** 2026-08-26T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Juvenile systemic sclerosis (jSSc) is a rare autoimmune condition with skin fibrosis and multi-organ involvement; autologous stem cell transplantation (ASCT) is an emerging therapy for severe, refractory disease. - The study collected PBMCs from three jSSc patients before ASCT and at 6, 12, and 24 months after ASCT, with healthy control samples for comparison. - Samples were profiled using **CITE-seq** (cellular indexing of transcriptomes and epitopes by sequencing) to capture joint RNA and protein signal at single-cell resolution. - Analyses focused on **monocytes** because of their recognized role in fibrosis-promoting inflammation in systemic sclerosis. - A longitudinal modeling approach regressed pseudobulked (log-scale) gene expression against time since ASCT to detect temporal trends across patients. - Key gene-level findings included decreased expression, after ASCT, of systemic sclerosis–linked genes such as **SERPINE1** in monocytes. - Pathway-level results showed elevated **NF-κB**–associated inflammatory signaling in jSSc monocytes at baseline versus healthy controls, with progressive decreases following ASCT. - Genes related to mitochondrial function and **oxidative phosphorylation** increased progressively after ASCT, suggesting a metabolic shift in monocytes posttransplant. - Compositional changes in monocyte subpopulations were observed and may have contributed to the longitudinal gene expression dynamics. - The study presents both immunologic insights into jSSc response to ASCT and a broadly applicable longitudinal single-cell modeling framework. The authors provided code on GitHub and reported funding sources; no competing interests were declared.
## Clinical Analysis & Structured Key Points
Longitudinal single-cell modeling reveals monocyte reprogramming in juvenile systemic sclerosis following autologous stem cell transplantation | bioRxiv Skip to main content New Results Longitudinal single-cell modeling reveals monocyte reprogramming in juvenile systemic sclerosis following autologous stem cell transplantation View ORCID Profile Julia K. Elrod , View ORCID Profile Anwesha Sanyal , Theresa Hutchins , View ORCID Profile F. William Townes , View ORCID Profile Kathryn S. Torok doi: https://doi.org/10.64898/2026.08.21.738279 Julia K. Elrod 1 Carnegie Mellon University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Julia K. Elrod Anwesha Sanyal 2 University of Pittsburgh Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Anwesha Sanyal Theresa Hutchins 2 University of Pittsburgh Find this author on Google Scholar Find this author on PubMed Search for this author on this site F. William Townes 1 Carnegie Mellon University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for F. William Townes Kathryn S. Torok 2 University of Pittsburgh Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kathryn S. Torok For correspondence: kathryn.torok{at}chp.edu Abstract Info/History Metrics Supplementary material Data/Code Preview PDF Abstract Juvenile systemic sclerosis (jSSc) is a rare autoimmune disease marked by skin fibrosis and multi-organ involvement. Autologous stem cell transplantation (ASCT) is an emerging therapy for severe, treatment-refractory jSSc, but its effects on immune cell dynamics remain poorly understood. PBMCs were collected from three patients with jSSc before ASCT and at 6, 12, and 24 months post-ASCT. Patient and healthy control samples were profiled using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq). We focused on monocytes, given their role in fibrosis-promoting inflammation. To detect longitudinal trends, pseudobulked gene expression (log scale) was regressed against time since ASCT. This approach identified widespread changes in jSSc monocytes, including decreased expression of systemic sclerosis-linked genes, such as SERPINE1. On the pathway level, NF-κB-associated inflammatory signaling was elevated in jSSc monocytes at baseline relative to healthy controls and decreased progressively post-ASCT. Genes related to mitochondrial function and oxidative phosphorylation progressively increased in expression after ASCT, suggesting a shift in metabolic state. Compositional changes in monocyte subpopulations were also identified and may have contributed to longitudinal gene expression patterns. Together, these findings characterize the dynamic immune changes in jSSc following ASCT and highlight a widely applicable longitudinal modeling framework for single-cell data. Competing Interest Statement The authors have declared no competing interest. Footnotes https://github.com/jkelrod97/jSSc-ASCT-longitudinal-monocytes Funder Information Declared National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) , R01 AR086434 , P50 AR060780 Department of Defense , USAMRDC W81XWH-21-1-0782 Seaman’s Children’s Hospital of Pittsburgh Scleroderma Reset awards Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted August 26, 2026. Download PDF Supplementary Material Data/Code 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. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Longitudinal single-cell modeling reveals monocyte reprogramming in juvenile systemic sclerosis following autologous stem cell transplantation Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Longitudinal single-cell modeling reveals monocyte reprogramming in juvenile systemic sclerosis following autologous stem cell transplantation Julia K. Elrod , Anwesha Sanyal , Theresa Hutchins , F. William Townes , Kathryn S. Torok bioRxiv 2026.08.21.738279; doi: https://doi.org/10.64898/2026.08.21.738279 Share This Article: Copy Citation Tools Longitudinal single-cell modeling reveals monocyte reprogramming in juvenile systemic sclerosis following autologous stem cell transplantation Julia K. Elrod , Anwesha Sanyal , Theresa Hutchins , F. William Townes , Kathryn S. Torok bioRxiv 2026.08.21.738279; doi: https://doi.org/10.64898/2026.08.21.738279 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 (7932) Biochemistry (18539) Bioengineering (14701) Bioinformatics (43919) Biophysics (22341) Cancer Biology (19465) Cell Biology (26636) Clinical Trials (138) Developmental Biology (13845) Ecology (20770) Epidemiology (2067) Evolutionary Biology (25202) Genetics (16047) Genomics (23311) Immunology (18502) Microbiology (42025) Molecular Biology (17860) Neuroscience (92421) Paleontology (691) Pathology (2953) Pharmacology and Toxicology (5045) Physiology (8025) Plant Biology (15814) Scientific Communication and Education (2089) Synthetic Biology (4517) Systems Biology (10146) Zoology (2367)
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