bone marrow niches
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Blood ◽  
2021 ◽  
Author(s):  
Zhuo Yu ◽  
Wenqian Yang ◽  
Xiaoxiao He ◽  
Chiqi Chen ◽  
Wenrui Li ◽  
...  

Bone marrow niche cells have been reported to fine-tune HSC stemness via direct interaction or secreted components. Nevertheless, how niche cells control HSC activities remains largely unknown. We previously showed that angiopoietin-like protein 2 (ANGPTL2) can support the ex vivo expansion of HSCs by binding to human leukocyte immunoglobulin-like receptor B2 (LILRB2). However, how ANGPTL2 from specific niche cell types regulates HSC activities under physiological conditions is still not clear. Herein, we generated an Angptl2-flox/flox transgenic mouse line and conditionally deleted Angptl2 expression in several niche cells, including Cdh5+ or Tie2+ endothelial cells, Prx1+ mesenchymal stem cells and Pf4+ megakaryocytes, to evaluate its role in the regulation of HSC fate. Interestingly, we demonstrated that only endothelial cell-derived ANGPTL2 and not ANGPTL2 from other niche cell types plays important roles in supporting repopulation capacity, quiescent status and niche localization. Mechanistically, ANGPTL2 enhances PPARD expression to transactivate G0s2 to sustain the perinuclear localization of nucleolin to prevent HSCs from entering the cell cycle. These findings reveal that endothelial cell-derived ANGPTL2 serves as a critical niche component to maintain HSC stemness, which may benefit the understanding of stem cell biology in bone marrow niches and the development of a unique strategy for the ex vivo expansion of HSCs.


Author(s):  
Lipeng Wang ◽  
Hao Zhang ◽  
Sicheng Wang ◽  
Xiao Chen ◽  
Jiacan Su

Recognized for nearly 100 years, bone marrow adipocytes (BMAs) form bone marrow niches that contain hematopoietic and bone cells, the roles of which have long been underestimated. Distinct from canonical white, brown, and beige adipocytes, BMAs derived from bone marrow mesenchymal stromal cells possess unique characteristics and functions. Recent single-cell sequencing studies have revealed the differentiation pathway, and seminal works support the tenet that BMAs are critical regulators in hematopoiesis, osteogenesis, and osteoclastogenesis. In this review, we discuss the origin and differentiation of BMAs, as well as the roles of BMAs in hematopoiesis, osteogenesis, osteoclastogenesis, and immune regulation. Overall, BMAs represent a novel target for bone marrow-related diseases, including osteoporosis and leukemia.


Biomaterials ◽  
2021 ◽  
pp. 121245
Author(s):  
Drew E. Glaser ◽  
Matthew B. Curtis ◽  
Peter A. Sariano ◽  
Zachary A. Rollins ◽  
Bhupinder S. Shergill ◽  
...  

Cell Reports ◽  
2021 ◽  
Vol 36 (8) ◽  
pp. 109618
Author(s):  
Marion Mesnieres ◽  
Anna-Marei Böhm ◽  
Nicolas Peredo ◽  
Dana Trompet ◽  
Roger Valle-Tenney ◽  
...  

2021 ◽  
Author(s):  
Tiancheng He ◽  
Weijie Zhang ◽  
Jiasong Li ◽  
Jianting Sheng ◽  
Xiang Zhang ◽  
...  

2021 ◽  
Vol 22 (4) ◽  
pp. 1881
Author(s):  
Takanori Yamaguchi ◽  
Eiji Kawamoto ◽  
Arong Gaowa ◽  
Eun Jeong Park ◽  
Motomu Shimaoka

Leukemia is a hematological malignancy that originates from hematopoietic stem cells in the bone marrow. Significant progress has made in understanding its pathogensis and in establishing chemotherapy and hematopoietic stem cell transplantation therapy (HSCT). However, while the successive development of new therapies, such as molecular-targeted therapy and immunotherapy, have resulted in remarkable advances, the fact remains that some patients still cannot be saved, and resistance to treatment and relapse are still problems that need to be solved in leukemia patients. The bone marrow (BM) niche is a microenvironment that includes hematopoietic stem cells and their supporting cells. Leukemia cells interact with bone marrow niches and modulate them, not only inducing molecular and functional changes but also switching to niches favored by leukemia cells. The latter are closely associated with leukemia progression, suppression of normal hematopoiesis, and chemotherapy resistance, which is precisely the area of ongoing study. Exosomes play an important role in cell-to-cell communication, not only with cells in close proximity but also with those more distant due to the nature of exosomal circulation via body fluids. In leukemia, exosomes play important roles in leukemogenesis, disease progression, and organ invasion, and their usefulness in the diagnosis and treatment of leukemia has recently been reported. The interaction between leukemia cell-derived exosomes and the BM microenvironment has received particular attention. Their interaction is believed to play a very important role; in addition to their diagnostic value, exosomes could serve as a marker for monitoring treatment efficacy and as an aid in overcoming drug resistance, among the many problems in leukemia patients that have yet to be overcome. In this paper, we will review bone marrow niches in leukemia, findings on leukemia-derived exosomes, and exosome-induced changes in bone marrow niches.


2021 ◽  
pp. jcs.250720
Author(s):  
Selda Ayhan ◽  
Emirhan Nemutlu ◽  
Duygu Uçkan Çetinkaya ◽  
Sedef Kır ◽  
Rıza Köksal Özgül

Bone marrow (BM) niches are special microenvironments that work in harmony with each other for the regulation and maintenance of hematopoiesis. The niche investigations have been remained limited with various model organisms and animal studies until today, therefore, little is known about different niches in healthy humans. In this study, the presence of different niches in BM by special harvesting method for the collection of BM from two different anatomical regions was investigated in the iliac crest of humans and identified metabolomic and transcriptomic profiles using comparative omic technologies. The main cellular pathways and corresponding transcripts and metabolites were identified. As a result, we found that the energy metabolism between the regions is different. This study provides basic broad data for regenerative medicine in terms of the design of the appropriate microenvironment for in-vitro hematopoietic niche modeling or providing the normal reference values that can be compared in hematological disease.


Hemato ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 43-63
Author(s):  
Masahiro Imamura

Impaired hematopoiesis is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Bone marrow aplasia and peripheral cytopenias arise from primary and secondary graft failure or primary and secondary poor graft function. Chimerism analysis is useful to discriminate these conditions. By determining the pathogenesis of impaired hematopoiesis, a timely and appropriate treatment can be performed. Hematopoietic system principally consists of hematopoietic stem cells and bone marrow microenvironment termed niches. Abnormality in hematopoietic stem and progenitor cells and/or abnormality in the relevant niches give rise to hematological diseases. Allo-HSCT is intended to cure each hematological disease, replacing abnormal hematopoietic stem cells and bone marrow niches with hematopoietic stem cells and bone marrow niches derived from normal donors. Therefore, treatment for graft failure and poor graft function after allo-HSCT is required to proceed based on determining the pathogenesis of impaired hematopoiesis. Recent progress in this area suggests promising treatment manipulations for graft failure and poor graft function.


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