Paul Simonson | PubMed Health

PubMed2026

Type 1 interferon perturbates clonal competition by reshaping human blood development.

Inflammation accelerates evolutionary dynamics of hematopoietic stem cells (HSCs) in clonal hematopoiesis and myeloid neoplasms. We studied HSCs, progenitors and immune cells from patients with myeloproliferative neoplasms at baseline and following interferon-α (IFNα) treatment, the only therapy to deplete mutated stem cells. We deployed single-cell multiomics methods that distinguish the IFNα effects on mutated stem cells from the admixed wild-type HSCs, with respect to their differentiation, transcriptomes, immunophenotypes and chromatin accessibility. IFNα simultaneously activated HSCs into two polarized states: a lymphoid progenitor expansion associated with an anti-inflammatory state and an inflammatory myeloid progenitor state derived from HSCs. The augmented lymphoid differentiation balanced the typical myeloproliferative-neoplasm-induced myeloid bias, associated with normalized blood counts. Somatic mutations modified the effects of IFNα on HSC differentiation and cell cycle entry rates. Clonal fitness upon IFNα exposure was due to resistance of CALR- or JAK2-mutated stem cells to differentiate into inflammatory myeloid progenitors.

Journal Article↗

PubMedDate not supplied

Modulation of an optical needle's reflectivity alters the average photon path through scattering media.

We introduce the concept of deliberate placement of absorbers to alter the average path of photons through tissue for a biomedical optical device. By changing the reflectivity of a needle that separates a source and detector, the average photon path through a turbid medium can be changed. Totally reflective needles have photon scattering density functions similar to a point source and detector in an infinite medium. An absorbing needle moves the average photon path of photons that reach the detector away from the needle. Thus, by modulating the reflectivity of the needle, it is possible to modify the sensitive volume, and simple tomography data should be possible. These results are confirmed by Monte Carlo simulations and experiment. Experiments include moving a black target relative to an optical "needle" and measuring the resulting intensity and phase lag of light reaching a detector at the distal end of the needle.

Biopsy↗