The bile acid receptor TGR5 regulates the hematopoietic support capacity of the bone marrow niche DOI Open Access
Alejandro Alonso‐Calleja, Alessia Perino, Frédérica Schyrr

et al.

Published: Jan. 24, 2024

The gut is an emerging regulator of bone marrow (BM) hematopoiesis and several signaling molecules are involved in this communication. Among them, bile acids (BAs), originally classified as lipid solubilizers, have emerged powerful that act a relay between the digestive system, microbiota rest body. function BAs relies on specific receptors, including Takeda-G-protein-receptor-5 (TGR5). TGR5 has potent regulatory effects immune cells, but its effect BM primary organ remains unknown. Here, we investigated young mice observed significant reduction adipose tissue (BMAT) upon loss TGR5, accompanied by enrichment adipocyte progenitors which translated into enhanced hematopoietic recovery transplantation. These findings open possibility modulating stromal support acting signaling.This work shows loss-of-function reduces regulated accelerates data highlight key player microenvironment.

Language: Английский

Metabolic regulation of skeletal cell fate and function DOI
Steve Stegen, Geert Carmeliet

Nature Reviews Endocrinology, Journal Year: 2024, Volume and Issue: 20(7), P. 399 - 413

Published: March 18, 2024

Language: Английский

Citations

33
Leptin receptor+ cells promote bone marrow innervation and regeneration by synthesizing nerve growth factor DOI Creative Commons
Xiang Gao, Malea M. Murphy,

James G. Peyer

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(12), P. 1746 - 1757

Published: Nov. 27, 2023

The bone marrow contains peripheral nerves that promote haematopoietic regeneration after irradiation or chemotherapy (myeloablation), but little is known about how this regulated. Here we found nerve growth factor (NGF) produced by leptin receptor-expressing (LepR+) stromal cells required to maintain fibres in adult marrow. In nerveless marrow, steady-state haematopoiesis was normal and vascular were impaired myeloablation. LepR+ cells, the adipocytes they gave rise to, increased NGF production myeloablation, promoting sprouting regeneration. Nerves promoted activating β2 β3 adrenergic receptor signalling potentially adipocytes, increasing their of multiple factors. Peripheral thus through a reciprocal relationship which sustain synthesizing increase factors cells.

Language: Английский

Citations

33
Skeletal stem and progenitor cells in bone development and repair DOI Creative Commons
Dana Trompet, Seppe Melis, Andrei S. Chagin

et al.

Journal of Bone and Mineral Research, Journal Year: 2024, Volume and Issue: unknown

Published: April 30, 2024

Abstract Bone development, growth, and repair are complex processes involving various cell types interactions, with central roles played by skeletal stem progenitor cells. Recent research brought new insights into the precursor populations that mediate intramembranous endochondral bone development. Later in life, many of cellular molecular mechanisms determining development reactivated upon fracture, powerful trauma-induced signaling cues triggering a variety postnatal stem/progenitor cells (SSPCs) residing near defect. Interestingly, this injury context, current evidence suggests fates both SSPCs differentiated can be considerably flexible dynamic, multiple sources activated to operate as functional progenitors generating chondrocytes and/or osteoblasts. The combined implementation vivo lineage tracing, surface marker-based selection, single-cell analyses, high-resolution situ imaging has strongly improved our diversity developmental reparative subsets, while also unveiling complexity their dynamics, hierarchies, relationships. Albeit incompletely understood at present, findings supporting flexibility possibly plasticity among osteogenic challenge classical dogma single primitive, self-renewing, multipotent driving tissue formation regeneration from apex hierarchical strictly unidirectional differentiation tree. We here review state field newest discoveries origin, identity, during discuss contributions adult SSPC fracture repair, reflect on dynamism relationships precursors lineages. Further directed unraveling heterogeneity capacities SSPCs, well regulatory fate functioning, will offer vital options for clinical translation toward compromised healing regenerative medicine.

Language: Английский

Citations

12
Alterations in Alzheimer's disease microglia transcriptome might be involved in bone pathophysiology DOI Creative Commons

Mohini Gharpure,

Sagar Vyavahare, Pankaj Ahluwalia

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 191, P. 106404 - 106404

Published: Jan. 4, 2024

Aging is a major risk factor for multiple chronic disorders in the elderly population, including Alzheimer's disease (AD) and Osteoporosis. AD progressive neurodegenerative characterized by memory loss. In addition to dementia, several studies have shown that patients experience an increased rate of musculoskeletal co-morbidities, such as osteoporosis. Since tissue-specific macrophages contribute both diseases, this study analyzed microglia transcriptome mice determine common gene signature involved osteoclast biology. After comparing differentially regulated genes from GEO data sets (GSE93824 GSE212277), there were 35 upregulated 89 downregulated genes. Of these genes, seven are known play important role bone homeostasis. CSF1, SPP1, FAM20C, Cst7 associated with osteoclastogenesis inflammation. Among LILRA6, MMP9, COL18A1 formation regulation. We further validated some (CSF1, Cst7, SPP1) cortex models. The dysregulation microglial might provide insights into co-occurrence osteoporosis offer potential therapeutic targets combat progression.

Language: Английский

Citations

10
Deep imaging of LepR+ stromal cells in optically cleared murine bone hemisections DOI Creative Commons
Yuehan Ni, Jun Wu, Fengqi Liu

et al.

Bone Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 12, 2025

Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional (3D) architecture of tissues and deciphering cellular spatial interactions under physiological pathological conditions. Deciphering interaction leptin receptor-expressing (LepR+) stromal cells other compartments in bone marrow crucial deeper understanding stem cell niche skeletal tissue. In this study, we introduce an optimized protocol 3D analysis tissues, enabling visualization hematopoietic cells, especially LepR+ within optically cleared hemisections. Our method preserves tissue extendable to sites such as calvaria vertebrae. The entails fixation, decalcification, cryosectioning reveal cavity. Completed approximately 12 days, process yields highly transparent that maintain genetically encoded or antibody-stained fluorescent signals. hemisections are compatible diverse antibody labeling strategies. Confocal microscopy these samples allows qualitative quantitative image using Aivia Bitplane Imaris software, assessing spectrum parameters. With proper storage, signal stained remains intact at least 2-3 months. This robust, straightforward implement, reproducible, offering valuable tool studies.

Language: Английский

Citations

1
Identification of genomic characteristics and selective signals in Guizhou black goat DOI Creative Commons

Lingle Chang,

Yundi Zheng,

Sheng Li

et al.

BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)

Published: Feb. 9, 2024

Abstract Background Guizhou black goat is one of the indigenous breeds in southwest region Guizhou, China, which an ordinary for mutton production. They are characterized by moderate body size, coat, favorite meat quality with tender and lower odor, tolerance cold crude feed. However, little known about genetic characteristics or variations underlying their important economic traits. Results Here, we resequenced whole genome from 30 unrelated individuals breeding five core farms. A total 9,835,610 SNPs were detected, 2,178,818 identified specifically this breed. The population structure analysis revealed that shared a common ancestry Shaanbei white cashmere (0.146), Yunshang (0.103), Iran (0.054), Moroccan (0.002). showed relatively higher diversity level linkage disequilibrium than other seven nucleotide diversity, decay, runs homozygosity. Based on F ST θ π values, 645, 813, 804 selected regions between goat, goats. Combined results XP-EHH, there 286, 322, 359 candidate genes, respectively. Functional annotation these genes potentially responsible immune response (e.g., CD28 , CD274 IL1A TLR2 SLC25A31 ), humility-cold resistance HBEGF SOSTDC1 ARNT COL4A1/2 EP300 traits CHUK GAB2 PLAAT3 growth DPYD CSF1 fertility METTL15 MEI1 visual function PANK2 NMNAT2 ) goat. Conclusion Our indicated had high genomic low genome. Selection signatures detected mainly related to development, quality, reproduction, disease resistance, humidity-cold These would provide basis further resource protection improvement very local

Language: Английский

Citations

8
Skeletal stem and progenitor cells in bone physiology, ageing and disease DOI
Seppe Melis, Dana Trompet, Andrei S. Chagin

et al.

Nature Reviews Endocrinology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 8, 2024

Language: Английский

Citations

7
Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics and Proteomic Imaging DOI Creative Commons
Shovik Bandyopadhyay,

Michael Duffy,

Kyung Jin Ahn

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 16, 2024

Abstract The bone marrow is the organ responsible for blood production. Diverse non-hematopoietic cells contribute essentially to hematopoiesis. However, these and their spatial organization remain largely uncharacterized as they have been technically challenging study in humans. Here, we used fresh femoral head samples performed single-cell RNA sequencing (scRNA-Seq) profile 29,325 enriched discover nine transcriptionally distinct subtypes. We next employed CO-detection by inDEXing (CODEX) multiplexed imaging of 18 individuals, including both healthy acute myeloid leukemia (AML) samples, spatially over one million single with a novel 53-antibody panel. discovered relatively hyperoxygenated arterio-endosteal niche early myelopoiesis, an adipocytic, but not endosteal or perivascular, hematopoietic stem progenitor cells. our atlas predict cell type labels new images predictions uncover mesenchymal stromal (MSC) expansion leukemic blast/MSC-enriched neighborhoods AML patient samples. Our work represents first comprehensive, spatially-resolved multiomic human will serve reference future investigation cellular interactions that drive

Language: Английский

Citations

5
Nutrient regulation of bone marrow adipose tissue: skeletal implications of weight loss DOI
Clifford J. Rosen, Mark C. Horowitz

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 19(11), P. 626 - 638

Published: Aug. 16, 2023

Language: Английский

Citations

10
Single-Cell Landscape of the Cochlea Revealed Cell-Type-Specific Diversification in Hipposideros armiger Based on PacBio Long-Read Sequencing DOI Creative Commons
Mingyue Bao, Xue Wang,

Xintong Li

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 211 - 211

Published: Feb. 1, 2025

Echolocation represents one of the most rapid adaptive sensorimotor modulation behaviors observed in mammals, establishing bats as evolutionarily successful mammals. Bats rely on high-frequency hearing for survival, but our understanding its cellular molecular basis is scattered and segmented. Herein, we constructed first single-cell transcriptomic landscape cochlea Hipposideros armiger, a CF-FM bat, using PacBio-optimized genome compared it with results obtained from unoptimized original genomes. Sixteen distinct cell types were distributed across five spatial regions cochlea. Notably, through hematoxylin eosin staining fluorescence situ hybridization, identified new spiral ganglion neuron (SGN) cells H. armiger. These SGN are likely critical auditory perception may have driven evolution this species. Furthermore, uncovered differentiation relationships among specific types, such transition supporting to hair cells. Using cochlear atlas reference, susceptible deafness-associated genes (in human) also identified. In summary, study provides novel insights into mechanisms underlying highlights potential candidate therapeutic interventions loss.

Language: Английский

Citations

0