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Alliance"],"accepted":{"date-parts":[[2024,11,6]]},"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>\n                    Cell plasticity (CP), describing a dynamic cell state, plays a crucial role in maintaining homeostasis during organ morphogenesis, regeneration, and trauma-to-repair biological process. Single-cell-omics datasets provide an unprecedented resource to empower CP analysis. Hematopoiesis offers fertile opportunities to develop quantitative methods for understanding CP. In this study, we generated high-quality lineage-negative single-cell RNA-sequencing datasets under various conditions and introduced a working pipeline named scPlasticity to interrogate na\u00efve and disturbed plasticity of hematopoietic stem and progenitor cells with mutational or environmental challenges. Using embedding methods UMAP or FA, a continuum of hematopoietic development is visually observed in wild type where the pipeline confirms a low\n                    <jats:italic>proportion of hybrid cells<\/jats:italic>\n                    (\n                    <jats:italic>\n                      <jats:bold>P<\/jats:bold>\n                    <\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>\n                        <jats:bold>hc<\/jats:bold>\n                      <\/jats:italic>\n                    <\/jats:sub>\n                    , with bias range: 0.4\u223c0.6) on a transition trajectory. Upon\n                    <jats:italic>Tet2<\/jats:italic>\n                    mutation, a driver of leukemia, or treatment of DSS, an inducer of colitis,\n                    <jats:italic>\n                      <jats:bold>P<\/jats:bold>\n                    <\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>\n                        <jats:bold>hc<\/jats:bold>\n                      <\/jats:italic>\n                    <\/jats:sub>\n                    is increased and plasticity of hematopoietic stem and progenitor cells was enhanced. We prioritized several transcription factors and signaling pathways, which are responsible for\n                    <jats:italic>\n                      <jats:bold>P<\/jats:bold>\n                    <\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>\n                        <jats:bold>hc<\/jats:bold>\n                      <\/jats:italic>\n                    <\/jats:sub>\n                    alterations. In silico perturbation suggests knocking out EGR regulons or pathways of IL-1R1 and \u03b2-adrenoreceptor partially reverses\n                    <jats:italic>\n                      <jats:bold>P<\/jats:bold>\n                    <\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>\n                        <jats:bold>hc<\/jats:bold>\n                      <\/jats:italic>\n                    <\/jats:sub>\n                    promoted by\n                    <jats:italic>Tet2<\/jats:italic>\n                    mutation and inflammation.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202402971","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T12:30:11Z","timestamp":1731501011000},"page":"e202402971","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Computing hematopoiesis plasticity in response to genetic mutations and environmental 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