Monocyte Lineage Expansion Drives Transcriptomic Individuality in Genetically Identical Armadillo Quadruplets

) quadruplets, we previously showed that allele-specific expression (ASE) imbalances provide a stable molecular fingerprint of individuality. Here, we test whether such transcriptomic individuality reflects functional biological differences. We profiled bulk blood RNA from five cohorts of genetically identical quadruplets across three time points, and found persistent gene-expression signatures that predict individual identity. Focusing on a highly variable cohort, we then performed single-cell RNA-seq and ATAC-seq. In this litter, the most stably distinct individual showed an expanded monocyte-lineage compartment and gene-expression programs enriched for inflammatory and differentiation pathways. These cell-type and regulatory differences were stable over time and robust to experimental leprosy infection. Together, our results link transcriptomic individuality to lasting differences in immune-cell composition, illustrating how early stochastic events can produce persistent, biologically meaningful divergence among genetically identical individuals.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-04-01
DOI
https://doi.org/10.64898/2026.03.30.715171
Primary Topic
Single-cell and spatial transcriptomics
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article
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article

Monocyte Lineage Expansion Drives Transcriptomic Individuality in Genetically Identical Armadillo Quadruplets

Frank M. Knight, Jesse A Gillis, Risa Karakida Kawaguchi, Linda B. Adams et al.
bioRxiv (Cold Spring Harbor Laboratory)
Single-cell and spatial transcriptomics
article

Monocyte Lineage Expansion Drives Transcriptomic Individuality in Genetically Identical Armadillo Quadruplets

Frank M. Knight, Jesse A Gillis, Risa Karakida Kawaguchi, Linda B. Adams, Maria T. Peña, Sara Ballouz, Leon French
article en

Abstract

) quadruplets, we previously showed that allele-specific expression (ASE) imbalances provide a stable molecular fingerprint of individuality. Here, we test whether such transcriptomic individuality reflects functional biological differences. We profiled bulk blood RNA from five cohorts of genetically identical quadruplets across three time points, and found persistent gene-expression signatures that predict individual identity. Focusing on a highly variable cohort, we then performed single-cell RNA-seq and ATAC-seq. In this litter, the most stably distinct individual showed an expanded monocyte-lineage compartment and gene-expression programs enriched for inflammatory and differentiation pathways. These cell-type and regulatory differences were stable over time and robust to experimental leprosy infection. Together, our results link transcriptomic individuality to lasting differences in immune-cell composition, illustrating how early stochastic events can produce persistent, biologically meaningful divergence among genetically identical individuals.

bioRxiv (Cold Spring Harbor Laboratory)
University of the Ozarks (US), Kyoto University (JP), Health Resources and Services Administration (US), Cold Spring Harbor Laboratory (US), UNSW Sydney (AU), Cellular Research (United States) (US), The University of Tokyo (JP)
Openalex Percentile: Top 31%
Single-cell and spatial transcriptomics
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Monocyte Lineage Expansion Drives Transcriptomic Individuality in Genetically Identical Armadillo Quadruplets — Frank M. Knight, Jesse A Gillis, et al. · bioRxiv (Cold Spring Harbor Laboratory) (2026) | TGRS Research Map | TGRS