Deciphering the Complexities of Adult Human Steady State and Stress-Induced Hematopoiesis: Progress and Challenges

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 671 - 671

Published: Jan. 14, 2025

Human hematopoietic stem cells (HSCs) have traditionally been viewed as self-renewing, multipotent with enormous potential in sustaining essential steady state blood and immune cell production throughout life. Indeed, around 86% (1011-1012) of new generated daily a healthy young human adult are origin. Therapeutically, HSCs contributed to over 1.5 million transplants (HCTs) globally, making this the most successful regenerative therapy date. We will commence review by briefly highlighting selected key achievements (from 1868 end 20th century) that accomplishment. Much our knowledge hematopoiesis is based on small animal models that, despite their importance, do not always recapitulate hematopoiesis. Given this, we critically progress challenges faced identifying tracing lineage differentiation trajectories, referring murine studies needed. Moving forward given dynamic can readily adjust variety stressors, then discuss recent research advances contributing understanding (i) which HSPCs maintain hematopoiesis, (ii) where these located, (iii) mechanisms come into play when homeostatic switches stress-induced or emergency

Language: Английский

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Adipose-Derived Stem Cell Specific Affinity Peptide-Modified Adipose Decellularized Scaffolds for Promoting Adipogenesis

ACS Biomaterials Science & Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Adipose-derived stem cells (ADSCs) are known to promote angiogenesis and adipogenesis. However, their limited ability efficiently target integrate into specific tissues poses a major challenge for ADSC-based therapies. In this study, we identified seven-amino acid peptide sequence (P7) with high specificity ADSCs using phage display technology. P7 was then covalently conjugated decellularized adipose-derived matrix (DAM), creating an "ADSC homing device" designed recruit both in vitro vivo. The P7-conjugated DAM significantly enhanced ADSC adhesion proliferation vitro. After being implanted rat subcutaneous tissue, immunofluorescence staining after 14 days revealed that recruited greater number of ADSCs, promoting adipogenesis the surrounding tissue. Moreover, CD206 immunostaining at indicated facilitated polarization macrophages M2 phenotype implantation site. These findings demonstrate has affinity its conjugation improves recruitment This approach holds great potential wide range applications material surface modification.

Language: Английский

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The role of genetic/epigenetic factors and microenvironment in hematopoietic stem cell ageing

Biogerontology, Journal Year: 2025, Volume and Issue: 26(2)

Published: March 22, 2025

Language: Английский

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Systemic deficits in lipid homeostasis promote aging-associated impairments in B cell progenitor development

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Abstract Organismal aging has been associated with diverse metabolic and functional changes across tissues. Within the immune system, key features of physiological hematopoietic cell include increased fat deposition in bone marrow, impaired stem progenitor (HSPC) function, a propensity towards myeloid differentiation. This shift lineage bias can lead to pre-malignant marrow conditions such as clonal hematopoiesis indeterminate potential (CHIP) or cytopenias undetermined significance (CCUS), frequently setting stage for subsequent development age-related cancers lymphoid lineages. Human also lipid alterations tissues, decreased phospholipid membrane fluidity that arises result saturated fatty acid (FA) accumulation decay n-3 polyunsaturated (PUFA) species by age 80 years, however extent which FA metabolism contributes is less clear. Here, comprehensive multi-omics analyses uncovered role PUFA biosynthesis gene, ELOVL2 , mouse human aging. Whole transcriptome RNA-sequencing studies complementary flow cytometric from aged Elovl2 mutant (enzyme-deficient) mice compared age-matched controls revealed global downregulation markers expression genes involved specifically B development. These unveiled CD79B, vital molecular regulator pro-B pre-B stage, putative surface biomarker whose loss accelerated The lipidome versus wild-type displayed significant biophysical properties cellular membranes. To investigate relevance these finding aging, single RNA-seq dataset HSPCs spectrum rare subpopulation (< 7%) CD34 + expresses healthy adult marrow. HSPC subset, along CD79B -expressing lymphoid-committed cells, were almost completely absent cells isolated elderly samples. Together, findings uncover new roles enzymes regulation function hematopoiesis. In addition, because systemic enzymatic activity resulted are lymphoproliferative neoplasms, this study sheds light on an intriguing pathway could be leveraged future novel therapeutic modality target blood other involving lineage.

Language: Английский

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Single-cell multiomics of pediatric BM reveals age-dependent differences in lineage differentiation linked to stromal cell heterogeneity

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

Published: Nov. 3, 2024

Abstract Childhood is critical for hematopoietic development and the onset of hematologic diseases. To explore changes from infancy through adolescence, we generated a multi-modal single-cell atlas capturing mRNA surface protein expression 90.710 bone marrow (BM) cells. This includes stem/progenitor cells mesenchymal stromal cells, seven pediatric individuals two young adults. We demonstrate that BM distinct adolescents/young adults (AYA), shifting B-lineage dominance in early childhood to myeloid T-lineage bias adolescence. uncover lymphoid progenitors (LyPs) subsets regulating this shift: CD127-positive LyPs with output, most abundant childhood, CD127-negative features, more common AYAs. Age-related composition signaling, mediated by IL-7 TGF-β1, correspond lineage shift. study provides an in-depth resource understanding healthy potential early-life perturbations underlying

Language: Английский

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Platelet Factor 4 (PF4) Regulates Hematopoietic Stem Cell Aging

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

Published: Nov. 27, 2024

Abstract Hematopoietic stem cells (HSCs) responsible for blood cell production and their bone marrow regulatory niches undergo age-related changes, impacting immune responses predisposing individuals to hematologic malignancies. Here, we show that the alterations of megakaryocytic niche associated downregulation Platelet Factor 4 (PF4) are pivotal mechanisms driving HSC aging. PF4-deficient mice display several phenotypes reminiscent accelerated aging, including lymphopenia, increased myeloid output, DNA damage, mimicking physiologically aged HSCs. Remarkably, recombinant PF4 administration restored old HSCs youthful functional characterized by improved polarity, reduced enhanced in vivo reconstitution capacity, balanced lineage output. Mechanistically, identified LDLR CXCR3 as receptors transmitting signal, with double knockout showing exacerbated aging similar mice. Furthermore, human across various age groups also respond signaling, highlighting its potential rejuvenating hematopoietic systems. These findings pave way targeted therapies aimed at reversing decline implications prevention or improvement course diseases. Key Points Age-related attrition is a central mechanism supplementation, acting on receptors, rejuvenates function

Language: Английский

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Systemic deficits in lipid homeostasis promote aging-associated impairments in B cell progenitor development

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

Published: Sept. 26, 2024

Organismal aging has been associated with diverse metabolic and functional changes across tissues. Within the immune system, key features of physiological hematopoietic cell include increased fat deposition in bone marrow, impaired stem progenitor (HSPC) function, a propensity towards myeloid differentiation. This shift lineage bias can lead to pre-malignant marrow conditions such as clonal hematopoiesis indeterminate potential (CHIP) or cytopenias undetermined significance (CCUS), frequently setting stage for subsequent development age-related cancers lymphoid lineages. At systemic well sub-cellular level, human also lipid alterations, decreased phospholipid membrane fluidity that arises result saturated fatty acid (FA) accumulation decay n-3 polyunsaturated (PUFA) species by age 80 years, however extent which FA metabolism contributes is less clear. Here, we performed comprehensive multi-omics analyses uncovered role PUFA biosynthesis gene,

Language: Английский

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