Biology subjects

Pena, M. T.

Publications and source records attributed to Pena, M. T..

3 recordsLinked to original sources

bioRxiv2026

Monocyte Lineage Expansion Drives Transcriptomic Individuality in Genetically Identical Armadillo Quadruplets

Genetic diversity shapes phenotypes, yet even genetically identical individuals differ. In nine-banded armadillo (Dasypus novemcinctus) 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. TeaserGenetically identical armadillo quadruplets are identifiable by transcriptomic signatures shaped by cellular composition variation.

molecular biology↗

bioRxiv2022

Parallel evolution of reduced cancer risk and tumor suppressor duplications in Xenarthra

The risk of developing cancer is correlated with body size and lifespan within species, but there is no correlation between cancer and either body size or lifespan between species indicating that large, long-lived species have evolved enhanced cancer protection mechanisms. Previously we showed that several large bodied Afrotherian lineages evolved reduced intrinsic cancer risk, particularly elephants and their extinct relatives (Proboscideans), coincident with pervasive duplication of tumor suppressor genes (Vazquez and Lynch 2021). Unexpectedly, we also found that Xenarthrans (sloths, armadillos, and anteaters) evolved very low intrinsic cancer risk. Here, we show that: 1) several Xenarthran lineages that independently evolved large bodies, long lifespans, and reduced intrinsic cancer risk; 2) reduced cancer risk in the stem lineages of Xenarthra and Pilosa occurred coincident with bursts of tumor suppressor gene duplications; 3) cells from sloths proliferate extremely slowly while Xenarthran cells induce apoptosis are very low levels of DNA damage; and 4) the prevalence of cancer is extremely low Xenarthrans, and cancer is nearly absent from armadillos. These data implicate the duplication of tumor suppressor genes in the evolution of remarkably large body sizes and decreased cancer risk in Xenarthrans and suggest they are a remarkably cancer resistant group of mammals. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=167 SRC="FIGDIR/small/502824v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@a98f15org.highwire.dtl.DTLVardef@1f0b859org.highwire.dtl.DTLVardef@d6ed7eorg.highwire.dtl.DTLVardef@81f3d5_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

bioRxiv2020

Both adaptive immunity and IL-1R1 dependent signals improve clearance of cytosolic virulent mycobacteria in vivo

Mycobacterium tuberculosis infections claim more than a million lives each year and better treatments or vaccines are required. A crucial pathogenicity factor is translocation from the phago-lysosomes to the cytosol upon phagocytosis by macrophages. The translocation from the phago-lysosome into the cytosol is an ESX-1 dependent process as previously shown in vitro. Here we show that in vivo, mycobacteria also translocate to the cytosol but mainly when host immunity is compromised. We observed only low numbers of cytosolic bacilli in mice, armadillo, zebrafish and patient material infected with M. tuberculosis, M. marinum or M. leprae. In contrast, when innate or adaptive immunity was compromised, as in SCID or IL-1R1 deficient mice, a significant number of cytosolic M. tuberculosis bacilli were detected in lungs of infected mice. Taken together, M. tuberculosis infection is controlled by adaptive immune responses as well as IL-1R1-mediated signals that result in clearance of cells containing cytosolic mycobacteria in vivo. ImportanceFor decades, Mycobacterium tuberculosis is one of the deathliest pathogens known. Despite infecting approximately one third of the human population, no effective treatment or vaccine is available. A crucial pathogenicity factor is the subcellular localization, as M. tuberculosis can translocate from the phago-lysosome to the cytosol in macrophages. The situation in vivo is more complicated. In this study we establish that high level cytosolic escape of mycobacteria can indeed occur in vivo, but mainly when host resistance is compromised. The IL-1 pathway is crucial for the control of the number of cytosolic mycobacteria. The establishment that immune signals result in clearance of cells containing cytosolic mycobacteria, connects two important fields: cell-biology and immunology which is vital for the understanding of the pathology of M. tuberculosis.

cell biology↗