Periarteriolar niches become inflamed in aging bone marrow, remodeling the stromal microenvironment and depleting lymphoid progenitors

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(11)

Published: March 10, 2025

In early postnatal and young adult bone marrow, Leptin receptor–expressing (LepR + ) stromal cells endothelial synthesize factors required for hematopoietic stem cell (HSC) maintenance, including Stem Cell Factor (SCF) Cxcl12. However, little is known about how these change during aging. We performed single-cell RNA sequencing of mouse marrow at 2, 12, 24 mo age. identified five transcriptionally distinct subsets LepR cells, all which expressed the highest levels Scf Cxcl12 in throughout life. aging SCF from but not continued to be necessary maintenance HSCs restricted progenitors. arteriolar other periarteriolar increasing interferon This increased numbers Sca1 Cxcl9 with an inflammatory gene signature depleted lymphoid progenitors, least some are also periarteriolar. The environment thus became particularly inflamed aging, remodeling microenvironment depleting progenitors interferon-dependent manner.

Language: Английский

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Organoid Models of Lymphoid Tissues

Organoids, Journal Year: 2025, Volume and Issue: 4(2), P. 7 - 7

Published: April 7, 2025

Lymphoid organs are critical for organizing the development of immune system, generating tolerance, and orchestrating adaptive response to foreign antigens. Defects in their structure function can lead immunodeficiency, hypersensitivity, cancer, or autoimmune diseases. To better understand these diseases assess potential therapies, complex models that recapitulate anatomy physiology tissues required. Organoid possess a number advantages, including 3D microarchitecture, scalability, personalization, which make them ideal modelling lymphoid related pathologies. Organoids have been developed both primary secondary tissues; however, several limitations, immature phenotypes incomplete stromal cell populations. Furthermore, organoids often heterogeneous function. Several organs, such as spleen, do not yet robust organoid models, offering opportunities breakthroughs field. Overall, will pave way rapid testing novel organ modelling, personalized medicine. This review summarizes current advances organ—bone marrow thymus—as well lymph node spleen.

Language: Английский

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Function of hematopoiesis and bone marrow niche in inflammation and non-hematopoietic diseases

Life Medicine, Journal Year: 2025, Volume and Issue: 4(3)

Published: March 26, 2025

Abstract Hematopoiesis and the behavior of hematopoietic stem progenitor cells (HSPCs) are regulated by bone marrow niche. Here, we introduce major niche cell types in their response to stress condition. We highlight adaptation inflammatory condition non-hematopoietic diseases, which not systematically summarized. These emerging data suggest targeting hematopoiesis may provide novel therapeutic target precisely control progression diseases.

Language: Английский

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Differential regulation of fetal bone marrow and liver hematopoiesis by yolk-sac-derived myeloid cells

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 14, 2025

Language: Английский

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Erythropoiesis in the mammalian embryo

Experimental Hematology, Journal Year: 2024, Volume and Issue: 136, P. 104283 - 104283

Published: July 22, 2024

Language: Английский

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Reassessing endothelial-to-mesenchymal transition in mouse bone marrow: insights from lineage tracing models

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 20, 2023

Endothelial cells (ECs) and bone marrow stromal (BMSCs) play crucial roles in supporting hematopoiesis hematopoietic regeneration. However, whether ECs are a source of BMSCs remains unclear. Here, we evaluate the contribution endothelial-to-mesenchymal transition to BMSC generation postnatal mice. Single-cell RNA sequencing identifies expressing markers Prrx1 Lepr; however, this could not be validated using Prrx1-Cre Lepr-Cre transgenic Additionally, only minority marked by EC lineage tracing models Cdh5-rtTA-tetO-Cre or Tek-CreERT2. Moreover, Cdh5+ Tek+ show distinct spatial distributions characteristic mesenchymal markers, suggestive their origination from different progenitors rather than CDH5+ TEK+ ECs. Furthermore, myeloablation induced 5-fluorouracil treatment does increase BMSCs. Our findings indicate that hardly convert during homeostasis myeloablation-induced regeneration, highlighting importance appropriate genetic conducting careful data interpretation studies concerning transition.

Language: Английский

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Endothelial-derived angiocrine factors as instructors of embryonic development

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: June 29, 2023

Blood vessels are well-known to play roles in organ development and repair, primarily owing their fundamental function delivering oxygen nutrients tissues promote growth homeostasis. Endothelial cells however not merely passive conduits for carrying blood. There is now evidence that endothelial of the vasculature actively regulate tissue-specific development, morphogenesis function, as well playing disease cancer. Angiocrine factors factors, cytokines, signaling molecules or other regulators produced directly from instruct a diverse range outcomes cellular microenvironment, critical mediators vascular control function. The angiocrine only beginning be uncovered fields such homeostasis, regeneration, organogenesis, stem-cell maintenance, cell differentiation tumour growth. While some cases specific factor involved these processes has been identified, many molecular identity factor(s) remain discovered, even though importance implicated. In this review, we will specifically focus on endothelial-derived instructing tissue organogenesis during embryonic perinatal development.

Language: Английский

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Endothelial heterogeneity in bone marrow: insights across development, adult life and leukemia

Leukemia, Journal Year: 2024, Volume and Issue: 39(1), P. 8 - 24

Published: Nov. 11, 2024

The central role of the endothelial microenvironment in orchestrating bone marrow (BM) homeostasis and hematopoietic support has been confirmed at various developmental stages adult life. BM vasculature is crucial mediating communication between parenchyma circulating blood, displaying remarkable heterogeneity structure function. While vascular cell diversity other tissues long recognized, molecular basis this phenomenon just now emerging. Over past decade, single-cell approaches microscopic observations have expanded our understanding vasculature. solely characterized for their paracrine properties past, recent advances revolutionized perception function, revealing distinct anatomical locations associated with diverse states. identification phenotypic differences normal pathological conditions therefore deepened dynamics impact on hematopoiesis health disease. In review, we highlight key milestones within during development, adulthood aging. We also explore how leukemia affects can take knowledge forward to improve clinical practices. By synthesizing existing literature, aim address unresolved questions outline future research directions.

Language: Английский

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Sinusoidal and lymphatic vessel growth is controlled by reciprocal VEGF-C–CDH5 inhibition

Nature Cardiovascular Research, Journal Year: 2022, Volume and Issue: 1(11), P. 1006 - 1021

Published: Nov. 11, 2022

Language: Английский

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Layered immunity and layered leukemogenicity: Developmentally restricted mechanisms of pediatric leukemia initiation

Immunological Reviews, Journal Year: 2023, Volume and Issue: 315(1), P. 197 - 215

Published: Jan. 2, 2023

Summary Hematopoietic stem cells (HSCs) and multipotent progenitor (MPPs) arise in successive waves during ontogeny, their properties change significantly throughout life. Ontological changes HSCs/MPPs underlie corresponding mechanisms of pediatric leukemia initiation. As HSCs MPPs progress from fetal to neonatal, juvenile adult stages life, they undergo transcriptional epigenetic reprogramming that modifies immune output meet age‐specific pathogenic challenges. Some exclusively HSCs/MPPs. We propose this layered immunity instructs cell fates a parallel leukemogenicity. Indeed, some leukemias, such as myelomonocytic leukemia, myeloid Down syndrome, infant pre‐B‐cell acute lymphoblastic are age‐restricted. They only present infancy or early childhood. These leukemias likely progenitors lose competence for transformation age. Other childhood non‐infant have mutation profiles common but rare morphologically similar leukemias. differences could reflect temporal mutagenesis how respond given at different ages. Interactions between leukemogenic mutations normal developmental switches offer potential targets therapy.

Language: Английский

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