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Czechowicz, A.

Publications and source records attributed to Czechowicz, A..

2 recordsLinked to original sources

Quantum Barcoding Bridges High-Dimensional Immune Phenotyping with Signaling Responses across Species

Cross-species immune profiling is limited by marker-panel size and antibody cross-reactivity. We benchmark Quantum Barcoding (QBC), a split-pool oligo-antibody assay, against mass cytometry in human and rhesus macaque blood and integrate separately measured cells using MARIO. The resulting computationally matched profiles carry 174 protein features. Population-frequency concordance was higher in humans (Pearson r = 0.92) than rhesus macaques (r = 0.55), and fusion resolved complementary lineage subsets. Unstimulated signaling conservation varied by lineage, with B-cell profiles correlated across species (Spearman {rho} = 0.70). In the primary PBMC-reference analysis, GM-CSF increased pSTAT5 in human monocytes and dendritic populations and rhesus dendritic cells. Network inference identified convergent pSTAT5-centered connectivity changes in human monocytes and rhesus dendritic cells, including pSTAT1-edge reversal and gained pSTAT3/pERK coupling. These results connect broad surface phenotypes to inferred signaling organization while retaining species- and population-specific differences.

systems biology↗

Clonal Level Lineage Commitment Pathways of Hematopoietic Stem Cells In Vivo

While hematopoietic stem cells (HSCs) have been extensively studied at the population level, little is known about the lineage commitment of individual clones. Here, we provide comprehensive maps of in vivo HSC clonal development in mice under homeostasis and after depletion of the endogenous hematopoietic system. Under homeostasis, all donor-derived HSC clones regenerate blood homogeneously throughout all measured stages and lineages of hematopoiesis. In contrast, after the hematopoietic system has been depleted by irradiation or by an anti-ckit antibody, only a small fraction of donor-derived HSC clones differentiates while dominantly expanding and exhibiting lineage bias. We identified the cellular origins of clonal dominance and lineage bias, and uncovered the lineage commitment pathways that lead HSC clones to differential blood production. This study reveals surprising alterations in HSC regulation by irradiation, and identifies the key hematopoiesis stages that may be manipulated to control blood production and balance.\n\nSIGNIFICANCE STATEMENTHematopoietic stem cells (HSCs) sustain daily blood production through a complex step-wise lineage commitment process. In this work, we present the first comprehensive study of HSC lineage commitment at the clonal level and identify new HSC regulatory mechanisms that are undetectable by conventional population level studies. First, we uncover distinct HSC clonal pathways that lead to differential blood production and imbalances. Second, we reveal that HSC regulation under physiological conditions is strikingly different from that after injury. Third, we present a comprehensive map of HSC activities in vivo at the clonal level.

systems biology↗