bims-mithem 2026-03-08 papers

Issue of 2026–03–08
four papers selected by
Tim van Tienhoven, Erasmus Medical Center

Dev Cell. 2026 Mar 02. pii: S1534-5807(26)00043-2. [Epub ahead of print]

Hematopoietic stem cells activate a latent differentiation pathway to facilitate recovery after 5-fluorouracil-induced myeloablation.

Zhen Zhang, Ben Jin, Chenyu You, Ya Li, Li Lin, Jianlong Sun.

Myeloablative chemotherapy induces hematopoietic regeneration, a process orchestrated by hematopoietic stem cells (HSCs). Although prior studies have documented enhanced HSC differentiation during this process, the temporal changes in HSC fate in response to such stress remain unclear. Here, we employed lineage tracing and mathematical modeling to investigate the cell-fate dynamics of Endothelial Protein C Receptor (EPCR)-high HSCs following 5-fluorouracil (5-FU)-induced myeloablation. Our analysis revealed a transient surge in HSC differentiation immediately after 5-FU treatment, generating primarily myeloid-biased multipotent progenitors (MPPs)-subsets that typically receive limited HSC input under steady-state conditions. Following this initial cell-fate switch, elevated HSC differentiation persisted but rapidly reverted to the homeostatic differentiation pattern observed in unperturbed hematopoiesis. Additionally, our data highlight a substantial contribution of MPPs to myeloid and lymphoid lineage regeneration following 5-FU challenge. Together, these findings delineate the sequential fate transitions adopted by HSCs during severe myeloablation and identify stage-specific differentiation patterns of HSCs in stress hematopoiesis.

Keywords: 5-fluorouracil; hematopoietic stem cell; lineage tracing; stress hematopoiesis

DOI: https://doi.org/10.1016/j.devcel.2026.02.003

J Immunol. 2026 Feb 09. pii: vkag006. [Epub ahead of print]215(2):

Constitutive and regulated marrow adipocytes do not actively inhibit B lymphopoiesis.

Encarnacion Montecino-Rodriguez, Erin Baker, Kenneth Dorshkind.

Adipocytes accumulate in the bone marrow with age. This has been proposed to trigger age-related changes in hematopoiesis that include a decline in B cell development. Bone marrow fat cells differ from adipocytes in other areas of the body and include 2 subsets termed constitutive and regulated adipocytes. These 2 types of marrow adipocytes have distinct properties and distribution across the skeleton. We assessed the contribution of each adipocyte subset to the loss of B cell progenitors and the age-related increase in hematopoietic stem cells (HSCs) and myeloid progenitors by quantifying their frequency and number in constitutive and regulated adipocyte containing bones from young and old animals. We also examined hematopoiesis in mice fed a high fat diet, which increases marrow adipose tissue, and quantified the expression of genes encoding inflammatory cytokines in constitutive and regulated adipocytes from young and old mice. The results indicated that marrow adipocytes do not actively drive the decline of B lymphopoiesis and other changes in hematopoiesis that occur with age. Instead, the findings support a model in which the age-related expansion of constitutive and regulated fat decreases marrow space available for blood cell production thereby reducing the number of cells from all lineages and stages of hematopoietic development.

Keywords: hematopoiesis; lymphopoiesis; marrow adipocytes

DOI: https://doi.org/10.1093/jimmun/vkag006

Nat Struct Mol Biol. 2026 Mar 05.

Function and regulation of the mitochondrial stress response.

Joshua B Sheetz, Srividya Chandrasekhar, Michael Rapé.

As mitochondria have crucial roles in metabolism and signaling, their structure and function must be continuously monitored and rapidly adjusted to meet cellular demands. Critical to this regulation is a conserved stress response that detects and alleviates challenges to mitochondrial integrity. Recent work has shown that mitochondrial stress often elicits simultaneous protective reactions that act in a coordinated and tightly regulated fashion to preserve this essential organelle. Here we review components, coordination and control within this comprehensive stress response and discuss how increased understanding of mitochondrial stress signaling is beginning to inform therapeutic approaches directed against diseases of high unmet need.

DOI: https://doi.org/10.1038/s41594-026-01769-9