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Abstract The epoch of reionization (EoR) offers a unique window into the dawn of galaxy formation, through which high-redshift galaxies can be studied by observations of both themselves and their impact on the intergalactic medium. Line intensity mapping (LIM) promises to explore cosmic reionization and its driving sources by measuring intensity fluctuations of emission lines tracing the cosmic gas in varying phases. Using LIMFAST, a novel seminumerical tool designed to self-consistently simulate LIM signals of multiple EoR probes, we investigate how building blocks of galaxy formation and evolution theory, such as feedback-regulated star formation and chemical enrichment, might be studied with multitracer LIM during the EoR. On galaxy scales, we show that the star formation law and the feedback associated with star formation can be indicated by both the shape and redshift evolution of LIM power spectra. For a baseline model of metal production that traces star formation, we find that lines highly sensitive to metallicity are generally better probes of galaxy formation models. On larger scales, we demonstrate that inferring ionized bubble sizes from cross-correlations between tracers of ionized and neutral gas requires a detailed understanding of the astrophysics that shape the line luminosity–halo mass relation. Despite various modeling and observational challenges, wide-area, multitracer LIM surveys will provide important high-redshift tests for the fundamentals of galaxy formation theory, especially the interplay between star formation and feedback by accessing statistically the entire low-mass population of galaxies as ideal laboratories, complementary to upcoming surveys of individual sources by new-generation telescopes. 

The pioneer transcription factor (TF) PU.1 controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing nonpioneer TFs to enter otherwise inaccessible genomic sites. PU.1 deficiency fatally arrests lymphopoiesis and myelopoiesis in mice, but human congenital PU.1 disorders have not previously been described. We studied six unrelated agammaglobulinemic patients, each harboring a heterozygous mutation (four de novo, two unphased) of SPI1, the gene encoding PU.1. Affected patients lacked circulating B cells and possessed few conventional dendritic cells. Introducing disease-similar SPI1 mutations into human hematopoietic stem and progenitor cells impaired early in vitro B cell and myeloid cell differentiation. Patient SPI1 mutations encoded destabilized PU.1 proteins unable to nuclear localize or bind target DNA. In PU.1-haploinsufficient pro–B cell lines, euchromatin was less accessible to nonpioneer TFs critical for B cell development, and gene expression patterns associated with the pro– to pre–B cell transition were undermined. Our findings molecularly describe a novel form of agammaglobulinemia and underscore PU.1’s critical, dose-dependent role as a hematopoietic euchromatin gatekeeper.