RESUMEN
The human bone marrow (BM) niche sustains hematopoiesis throughout life. We present a method for generating complex BM-like organoids (BMOs) from human induced pluripotent stem cells (iPSCs). BMOs consist of key cell types that self-organize into spatially defined three-dimensional structures mimicking cellular, structural and molecular characteristics of the hematopoietic microenvironment. Functional properties of BMOs include the presence of an in vivo-like vascular network, the presence of multipotent mesenchymal stem/progenitor cells, the support of neutrophil differentiation and responsiveness to inflammatory stimuli. Single-cell RNA sequencing revealed a heterocellular composition including the presence of a hematopoietic stem/progenitor (HSPC) cluster expressing genes of fetal HSCs. BMO-derived HSPCs also exhibited lymphoid potential and a subset demonstrated transient engraftment potential upon xenotransplantation in mice. We show that the BMOs could enable the modeling of hematopoietic developmental aspects and inborn errors of hematopoiesis, as shown for human VPS45 deficiency. Thus, iPSC-derived BMOs serve as a physiologically relevant in vitro model of the human BM microenvironment to study hematopoietic development and BM diseases.
Asunto(s)
Diferenciación Celular , Hematopoyesis , Células Madre Pluripotentes Inducidas , Organoides , Humanos , Organoides/citología , Organoides/metabolismo , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Animales , Ratones , Células Madre Hematopoyéticas/citología , Médula Ósea/metabolismo , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Técnicas de Cultivo de Célula/métodos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismoRESUMEN
In the context of experimental advances in the realization of artificial magnetic fields in quantum gases, we discuss feasible schemes to extend measurements of the Hall polarization to a study of the Hall voltage, allowing for direct comparison with solid state systems. Specifically, for the paradigmatic example of interacting flux ladders, we report on characteristic zero crossings and a remarkable robustness of the Hall voltage with respect to interaction strengths, particle fillings, and ladder geometries, which is unobservable in the Hall polarization. Moreover, we investigate the site-resolved Hall response in spatially inhomogeneous quantum phases.