Nature Outlook |

Blood

Blood is the epicentre of much biomedical research, from fighting disease to creating artificial substitutes for this vital fluid. This Outlook discusses topics including a gene-editing treatment for sickle-cell disease and keeping the blood supply safe from pathogens such as Zika virus.

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When threats emerge to the blood supply, public-health officials must make difficult decisions to reduce the risk of infections being transmitted by transfusions.

Outlook | | Nature

Bloodstain pattern analysis is used by forensic scientists to help reconstruct violent crimes. Efforts are underway to root the often subjective practice in science.

Outlook | | Nature

Related articles

Matthew Porteus and colleagues develop a method to improve gene editing for correction of β-haemoglobinopathies such as sickle cell disease and β-thalassaemia. By optimizing delivery and CRISPR-based homologous recombination gene correction, scaling the genome editing protocol, and including a reporter gene to enrich for edited cell populations, the authors can increase the number of corrected long-term haematopoietic stem cells ex vivo that can retain their functionality after transplantation. Initial testing suggests that this strategy could be further developed for clinical implementation.

Article | | Nature

Obtaining functional human haematopoietic stem cells (HSCs) from differentiated pluripotent stem cells (PSCs) is proving a challenge for the field. George Daley and colleagues used a morphogen-based approach to differentiate human PSCs to the haemogenic endothelium, where endothelial cells and HSCs commonly originate. They then screened 26 candidate HSC-specifying transcription factors for their ability to confer multi-lineage blood engraftment to the haemogenic endothelial cells when transplanted into mice. They defined a set of seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that were sufficient to allow engraftment of myeloid, B and T cells in primary and secondary murine recipients. The cells obtained could one day enable researchers to model haematopoietic disease in humanized mice. Elsewhere in this issue, Shahin Rafii and colleagues reprogrammed in vitro mouse adult endothelial cells into mouse engraftable haematopoietic stem cells displaying some key functional properties.

Article | | Nature

The transition pathways of endothelial cells into haematopoietic stem cells remain undefined. Shahin Rafii and colleagues reprogrammed in vitro mouse adult endothelial cells into mouse engraftable haematopoietic stem cells which display the range of functional properties expected from true haematopoietic stem cells. They use a sequential approach to express transcription factors known to participate in the induction of haematopoiesis from the embryonic endothelium, as well as an endothelial cell line that acts as the vascular niche to provide the required signals. The reprogramed cells display single-cell and multilineage properties, long-term self-renewal and reconstitute T cell adaptive immune function. Converting endothelial cells into functional and self-renewing haematopoietic stem cells could open up treatment opportunities for haematological disorders, the authors suggest. Elsewhere in this issue, George Daley and colleagues differentiated human pluripotent stem cells to the haemogenic endothelium by expressing a set of transcription factors that regulate hematopoiesis.

Article | | Nature

Circulating tumour DNA (ctDNA) has proven useful for detecting and monitoring cancer progression from plasma samples. The authors have applied a bespoke multiplex-PCR next-generation sequencing approach to profile ctDNA in the prospective TRACERx lung cancer clinical trial study. The assay tracks clonal and subclonal variants, in pre- and post-surgery samples. In pre-surgery samples ctDNA detection is associated with histological subtype and other pathological variables and correlates with tumour volume. Blinded longitudinal profiling suggests that ctDNA detection also associates with relapse, and provides insight into the evolutionary patterns of tumour cell subclones during progression. These results advance our understanding of how liquid biopsies can be applied clinically to improve monitoring of cancer.

News & Views | | Nature

Disseminated intravascular coagulation (DIC) is a medical emergency that can be caused by infectious or non-infectious conditions. The mechanisms underlying DIC — highlighted in this PrimeView — are an imbalance in the factors that control haemostasis.

PrimeView | | Nature Reviews Disease Primers

Disseminated intravascular coagulation can be caused by various infectious and non-infectious insults, such as sepsis and trauma, respectively. It is characterized by the widespread activation of coagulation and, depending on the underlying condition, can manifest as bleeding and/or thrombosis.

Primer | | Nature Reviews Disease Primers

Owing to a lack of objective diagnostic tools, the diagnosis of mild traumatic brain injury (TBI) and related conditions, such as postconcussive syndrome and chronic traumatic encephalopathy must be made on clinical grounds. Here, Zetterberg and Blennow review the most recent developments in search for biomarkers for mild TBI and related conditions.

Review Article | | Nature Reviews Neurology