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Tan, T.-K.

Publications and source records attributed to Tan, T.-K..

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↗

Large-scale in vivo CRISPR screens identify SAGA complex members as a key regulators of HSC lineage commitment and aging

The biological mechanisms that sustain the vast blood production required for healthy life remain incompletely understood. To search for novel regulators of hematopoiesis, we performed genome-wide in vivo hematopoietic stem cell (HSC)-based CRISPR knockout screens for regulators of hematopoiesis. We discovered SAGA complex members, including Tada2b and Taf5l, as key regulators of hematopoiesis. Loss of Tada2b or Taf5l strongly inhibited hematopoiesis in vivo, led to a buildup of immature hematopoietic cells in the bone marrow, and was associated with upregulation of interferon pathway genes. Loss of these factors also enhanced the cell outgrowth and the interferon pathway in an in vivo human myelodysplastic syndrome model, suggesting that loss of SAGA complex activity could contribute to hematological disease progression. In summary, this study has identified the SAGA complex as an important regulator of hematopoiesis.

genetics↗