Ever-evolving insights into the cellular and molecular drivers of lymphoid cell development.

Lymphocytes play a critical role in adaptive immunity and defense mechanisms, but the molecular mechanisms by which hematopoietic stem and progenitor cells differentiate into T and B lymphocytes are not fully established. Pioneer studies identify several transcription factors essential for lymphoid lineage determination. Yet, many questions remain unanswered about how these transcription factors interact with each other and with chromatin at different developmental stages.

A time- and single-cell-resolved model of murine bone marrow hematopoiesis.

The paradigmatic hematopoietic tree model is increasingly recognized to be limited, as it is based on heterogeneous populations largely defined by non-homeostatic assays testing cell fate potentials. Here, we combine persistent labeling with time-series single-cell RNA sequencing to build a real-time, quantitative model of in vivo tissue dynamics for murine bone marrow hematopoiesis. We couple cascading single-cell expression patterns with dynamic changes in differentiation and growth speeds.

Intravital Microscopy for Hematopoietic Studies.

The bone marrow (BM) is home to numerous cell types arising from hematopoietic stem cells (HSCs) and nonhematopoietic mesenchymal stem cells, as well as stromal cell components. Together they form the BM microenvironment or HSC niche. HSCs critically depend on signaling from these niches to function and survive in the long term.

mA RNA modifications: Key regulators of normal and malignant hematopoiesis.

Post-transcriptional RNA modifications determine RNA fate by influencing numerous processes such as translation, decay and localization. One of the most abundant RNA modifications is N-methyladenoside (mA), which has been shown to be important in healthy as well as malignant hematopoiesis. Several proteins representing key players in mA RNA biology, such as mA writers, erasers and readers, were recently reported to be essential for hematopoietic stem cell (HSC) function.

Hematopoietic stem cell gene editing and expansion: State-of-the-art technologies and recent applications.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for a range of hematological diseases, from leukemias to immunodeficiencies and anemias. The aim in using HSCT is to replace a patient's dysfunctional blood system with a functional one by transplanting healthy hematopoietic stem cells (HSCs). HSCs may be collected from a healthy donor (for allogeneic HSCT) or from the patient for genetic correction (for autologous HSCT gene therapies).

Blood and immune development in human fetal bone marrow and Down syndrome.

Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11-12 weeks after conception, yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and newborn. Here we detail the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression.

Intravital Imaging of Bone Marrow Niches.

Haematopoietic stem cells (HSCs) are instrumental in driving the generation of mature blood cells, essential for various functions including immune defense and tissue remodeling. They reside within a specialised bone marrow (BM) microenvironment , or niche, composed of cellular and chemical components that play key roles in regulating long-term HSC function and survival. While flow cytometry methods have significantly advanced studies of hematopoietic cells, enabling their quantification in steady-state and perturbed situations, we are still learning about the specific BM microenvironments that support distinct lineages and how their niches are altered under stress and with age.

Manipulating niche composition limits damage to haematopoietic stem cells during Plasmodium infection.

Severe infections are a major stress on haematopoiesis, where the consequences for haematopoietic stem cells (HSCs) have only recently started to emerge. HSC function critically depends on the integrity of complex bone marrow (BM) niches; however, what role the BM microenvironment plays in mediating the effects of infection on HSCs remains an open question. Here, using a murine model of malaria and combining single-cell RNA sequencing, mathematical modelling, transplantation assays and intravital microscopy, we show that haematopoiesis is reprogrammed upon infection, whereby the HSC compartment turns over substantially faster than at steady-state and HSC function is drastically affected.

Targeting adhesion to the vascular niche to improve therapy for acute myeloid leukemia.

Niche hijack by malignant cells is considered to be a prominent cause of disease relapse. Barbier and colleagues uncover (E)-selectin as a novel mediator of malignant cell survival and regeneration which, upon blockade, has the potential to significantly improve therapeutic outcomes.

Author Correction: Dynamic responses of the haematopoietic stem cell niche to diverse stresses.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Dynamic responses of the haematopoietic stem cell niche to diverse stresses.

Adult haematopoietic stem cells (HSCs) mainly reside in the bone marrow, where stromal and haematopoietic cells regulate their function. The steady state HSC niche has been extensively studied. In this Review, we focus on how bone marrow microenvironment components respond to different insults including inflammation, malignant haematopoiesis and chemotherapy.

Systematic tracking of altered haematopoiesis during sporozoite-mediated malaria development reveals multiple response points.

Haematopoiesis is the complex developmental process that maintains the turnover of all blood cell lineages. It critically depends on the correct functioning of rare, quiescent haematopoietic stem cells (HSCs) and more numerous, HSC-derived, highly proliferative and differentiating haematopoietic progenitor cells (HPCs). Infection is known to affect HSCs, with severe and chronic inflammatory stimuli leading to stem cell pool depletion, while acute, non-lethal infections exert transient and even potentiating effects.

Increased production of retinoic acid by intestinal macrophages contributes to their inflammatory phenotype in patients with Crohn's disease.

Background & Aims: Reduced generation of all-trans retinoic acid (RA) by CD103(+) intestinal dendritic cells (DCs) is linked to intestinal inflammation in mice. However, the role of RA in intestinal inflammation in humans is unclear. We investigated which antigen-presenting cells (APCs) produce RA in the human intestine and whether generation of RA is reduced in patients with Crohn's disease (CD).