Self-organization of embryonic stem cells into a reproducible embryo model through epigenome editing.

Embryonic stem cells (ESCs) can self-organize in vitro into developmental patterns with spatial organization and molecular similarity to that of early embryonic stages. This self-organization of ESCs requires transmission of signaling cues, via addition of small molecule chemicals or recombinant proteins, to induce distinct embryonic cellular fates and subsequent assembly into structures that can mimic aspects of early embryonic development. During natural embryonic development, different embryonic cell types co-develop together, where each cell type expresses specific fate-inducing transcription factors through activation of non-coding regulatory elements and interactions with neighboring cells. However, previous studies have not fully explored the possibility of engineering endogenous regulatory elements to shape self-organization of ESCs into spatially-ordered embryo models. Here, we hypothesized that cell-intrinsic activation of a minimum number of such endogenous regulatory elements is sufficient to self-organize ESCs into early embryonic models. Our results show that CRISPR-based activation (CRISPRa) of only two endogenous regulatory elements in the genome of pluripotent stem cells is sufficient to generate embryonic patterns that show spatial and molecular resemblance to that of pre-gastrulation mouse embryonic development. Quantitative single-cell live fluorescent imaging showed that the emergence of spatially-ordered embryonic patterns happens through the intrinsic induction of cell fate that leads to an orchestrated collective cellular motion. Based on these results, we propose a straightforward approach to efficiently form 3D embryo models through intrinsic CRISPRa-based epigenome editing and independent of external signaling cues. CRISPRa-Programmed Embryo Models (CPEMs) show highly consistent composition of major embryonic cell types that are spatially-organized, with nearly 80% of the structures forming an embryonic cavity. Single cell transcriptomics confirmed the presence of main embryonic cell types in CPEMs with transcriptional similarity to pre-gastrulation mouse embryos and revealed novel signaling communication links between different embryonic cell types. Our findings offer a programmable embryo model and demonstrate that minimum intrinsic epigenome editing is sufficient to self-organize ESCs into highly consistent pre-gastrulation embryo models.

Symptoms of another life: time, possibility, and domestic relations in Chile's credit economy.

In this article, I explore the synergy and disjunctures of the consumer credit system and care for the mentally ill and addicted in the lifeworlds of the urban poor in Santiago, Chile. In Chile, the expansion of the credit system has had a double-edged effect on the poor. Although it produces perpetual indebtedness, it also is a resource amid unstable labor. Following an extended family over several years, this article examines how women take up credit through a wider field of domestic relations and institutions to care for kin with mental illness and addiction within the home. Such gestures of care enact a temporality of waiting, allowing different, but unpredictable, aspects of others to emerge. Through longitudinal ethnographic research with this family, I demonstrate both how possibility is actualized within the home as symptoms of illness and forms of domestic violence, and how a wider network of dependencies­from neighbors to lending institutions­shapes the temporality of relations within the home. Such a study of care in relation to the credit economy may offer other analytic perspectives on discourses of individualism, consumerism, and cost-effectiveness accompanying the expansion of consumer credit as they are absorbed into the everyday.

The work of indebtedness: the traumatic present of late capitalist Chile.

In political and biomedical discourses, "posttraumatic stress disorder" has become a set of organizing concepts for trauma and traumatic memory. These concepts, however, are predicated on an understanding of traumatic memory as a discrete etiological event that, when reexperienced, is productive of symptoms. In this essay, I explore alternative framings of trauma that arise out of historical changes in political economic language and from experiences of monetary, historical, and affective indebtedness in Santiago, Chile. This ethnographic research is based in an historically leftist población (poor urban sector) and follows the interwoven narratives of a formerly exiled communist militant and her adopted daughter. Throughout this essay, I describe the mother's attempts to inhabit an untimely language of socialist politics and the daughter's rejection of both this language and her mother's pain. I elaborate on how these attempts are products of and productive of monetary and intersubjective indebtedness in a neoliberal present. By describing the differing historical languages inhabited by these subjects, I attempt to evoke an understanding of trauma not as an individual possession or etiological event, but rather as a referential dissonance in the neoliberal context. This referential dissonance emerges from the gap between the historical languages that inform subjectivities. I explore how such a gap can create contexts in which the everyday itself both threatens the disarticulation of the subject and produces injurious affective relationships. In this way, I interrogate relationships between trauma, recovery, and the everyday.