scholarly journals Biomechanical cues as master regulators of hematopoietic stem cell fate

2021 ◽  
Author(s):  
Honghu Li ◽  
Qian Luo ◽  
Wei Shan ◽  
Shuyang Cai ◽  
Ruxiu Tie ◽  
...  
Keyword(s):  
Cell Fate ◽  
Ex Vivo ◽  
Signaling Networks ◽  
Matrix Stiffness ◽  
Hematopoietic Stem ◽  
Stem Cell Fate ◽  
Master Regulators ◽  
Cellular Processes ◽  
Extracellular Matrix Stiffness ◽  
Bona Fide

AbstractHematopoietic stem cells (HSCs) perceive both soluble signals and biomechanical inputs from their microenvironment and cells themselves. Emerging as critical regulators of the blood program, biomechanical cues such as extracellular matrix stiffness, fluid mechanical stress, confined adhesiveness, and cell-intrinsic forces modulate multiple capacities of HSCs through mechanotransduction. In recent years, research has furthered the scientific community’s perception of mechano-based signaling networks in the regulation of several cellular processes. However, the underlying molecular details of the biomechanical regulatory paradigm in HSCs remain poorly elucidated and researchers are still lacking in the ability to produce bona fide HSCs ex vivo for clinical use. This review presents an overview of the mechanical control of both embryonic and adult HSCs, discusses some recent insights into the mechanisms of mechanosensing and mechanotransduction, and highlights the application of mechanical cues aiming at HSC expansion or differentiation.

scholarly journals Towards Mimicking the Fetal Liver Niche: The Influence of Elasticity and Oxygen Tension on Hematopoietic Stem/Progenitor Cells Cultured in 3D Fibrin Hydrogels

2020 ◽  
Vol 21 (17) ◽  
pp. 6367
Author(s):  
Christian Garcia-Abrego ◽  
Samantha Zaunz ◽  
Burak Toprakhisar ◽  
Ramesh Subramani ◽  
Olivier Deschaume ◽  
...  
Keyword(s):  
Suspension Culture ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Oxygen Tension ◽  
Fetal Liver ◽  
Culture Conditions ◽  
Matrix Stiffness ◽  
Hematopoietic Stem ◽  
Stem Cell Fate ◽  
Bm Niche

Hematopoietic stem/progenitor cells (HSPCs) are responsible for the generation of blood cells throughout life. It is believed that, in addition to soluble cytokines and niche cells, biophysical cues like elasticity and oxygen tension are responsible for the orchestration of stem cell fate. Although several studies have examined the effects of bone marrow (BM) niche elasticity on HSPC behavior, no study has yet investigated the effects of the elasticity of other niche sites like the fetal liver (FL), where HSPCs expand more extensively. In this study, we evaluated the effect of matrix stiffness values similar to those of the FL on BM-derived HSPC expansion. We first characterized the elastic modulus of murine FL tissue at embryonic day E14.5. Fibrin hydrogels with similar stiffness values as the FL (soft hydrogels) were compared with stiffer fibrin hydrogels (hard hydrogels) and with suspension culture. We evaluated the expansion of total nucleated cells (TNCs), Lin−/cKit+ cells, HSPCs (Lin−/Sca+/cKit+ (LSK) cells), and hematopoietic stem cells (HSCs: LSK- Signaling Lymphocyte Activated Molecule (LSK-SLAM) cells) when cultured in 5% O2 (hypoxia) or in normoxia. After 10 days, there was a significant expansion of TNCs and LSK cells in all culture conditions at both levels of oxygen tension. LSK cells expanded more in suspension culture than in both fibrin hydrogels, whereas TNCs expanded more in suspension culture and in soft hydrogels than in hard hydrogels, particularly in normoxia. The number of LSK-SLAM cells was maintained in suspension culture and in the soft hydrogels but not in the hard hydrogels. Our results indicate that both suspension culture and fibrin hydrogels allow for the expansion of HSPCs and more differentiated progeny whereas stiff environments may compromise LSK-SLAM cell expansion. This suggests that further research using softer hydrogels with stiffness values closer to the FL niche is warranted.

scholarly journals The physical microenvironment of hematopoietic stem cells and its emerging roles in engineering applications

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Pan Zhang ◽  
Chen Zhang ◽  
Jing Li ◽  
Jiyang Han ◽  
Xiru Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Cell Fate ◽  
Hematopoietic Stem Cell ◽  
Ex Vivo ◽  
Hematopoietic Stem ◽  
Stem Cell Fate ◽  
Stem Cell Engineering

AbstractStem cells are considered the fundamental underpinnings of tissue biology. The stem cell microenvironment provides factors and elements that play significant roles in controlling the cell fate direction. The bone marrow is an important environment for functional hematopoietic stem cells in adults. Remarkable progress has been achieved in the area of hematopoietic stem cell fate modulation based on the recognition of biochemical factors provided by bone marrow niches. In this review, we focus on emerging evidence that hematopoietic stem cell fate is altered in response to a variety of microenvironmental physical cues, such as geometric properties, matrix stiffness, and mechanical forces. Based on knowledge of these biophysical cues, recent developments in harnessing hematopoietic stem cell niches ex vivo are also discussed. A comprehensive understanding of cell microenvironments helps provide mechanistic insights into pathophysiological mechanisms and underlies biomaterial-based hematopoietic stem cell engineering.

scholarly journals Non-viral ex vivo genome-editing in mouse bona fide hematopoietic stem cells with CRISPR/Cas9

2021 ◽  
Vol 20 ◽  
pp. 451-462
Author(s):  
Suvd Byambaa ◽  
Hideki Uosaki ◽  
Tsukasa Ohmori ◽  
Hiromasa Hara ◽  
Hitoshi Endo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Genome Editing ◽  
Ex Vivo ◽  
Hematopoietic Stem ◽  
Bona Fide

Signal control of hematopoietic stem cell fate: Wnt, Notch, and Hedgehog as the usual suspects

2008 ◽  
Vol 15 (4) ◽  
pp. 319-325 ◽  
Author(s):  
Clint Campbell ◽  
Ruth M Risueno ◽  
Simona Salati ◽  
Borhane Guezguez ◽  
Mickie Bhatia
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Hematopoietic Stem Cell ◽  
Signal Control ◽  
Hematopoietic Stem ◽  
Stem Cell Fate

Asymmetric organelle inheritance predicts human blood stem cell fate

Blood ◽  
2021 ◽  
Author(s):  
Dirk Loeffler ◽  
Florin Schneiter ◽  
Weijia Wang ◽  
Arne Wehling ◽  
Tobias Kull ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Cell Fate ◽  
Human Blood ◽  
Asymmetric Cell Division ◽  
Cell Fates ◽  
Hematopoietic Stem ◽  
Stem Cell Fate ◽  
Blood Stem Cells

Understanding human hematopoietic stem cell fate control is important for their improved therapeutic manipulation. Asymmetric cell division, the asymmetric inheritance of factors during division instructing future daughter cell fates, was recently described in mouse blood stem cells. In human blood stem cells, the possible existence of asymmetric cell division remained unclear due to technical challenges in its direct observation. Here, we use long-term quantitative single-cell imaging to show that lysosomes and active mitochondria are asymmetrically inherited in human blood stem cells and that their inheritance is a coordinated, non-random process. Furthermore, multiple additional organelles, including autophagosomes, mitophagosomes, autolysosomes and recycling endosomes show preferential asymmetric co-segregation with lysosomes. Importantly, asymmetric lysosomal inheritance predicts future asymmetric daughter cell cycle length, differentiation and stem cell marker expression, while asymmetric inheritance of active mitochondria correlates with daughter metabolic activity. Hence, human hematopoietic stem cell fates are regulated by asymmetric cell division, with both mechanistic evolutionary conservation and differences to the mouse system.

scholarly journals Matrix Mechanosensation in the Erythroid and Megakaryocytic Lineages

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 894
Author(s):  
Christina M. Ward ◽  
Katya Ravid
Keyword(s):  
Bone Marrow ◽  
Ion Channels ◽  
Cell Fate ◽  
Biomechanical Properties ◽  
Structural Proteins ◽  
Matrix Stiffness ◽  
Surface Adhesion ◽  
Hematopoietic Stem ◽  
Mechanosensitive Ion Channels ◽  
Sense And Respond

The biomechanical properties of the bone marrow microenvironment emerge from a combination of interactions between various extracellular matrix (ECM) structural proteins and soluble factors. Matrix stiffness directs stem cell fate, and both bone marrow stromal and hematopoietic cells respond to biophysical cues. Within the bone marrow, the megakaryoblasts and erythroblasts are thought to originate from a common progenitor, giving rise to fully mature magakaryocytes (the platelet precursors) and erythrocytes. Erythroid and megakaryocytic progenitors sense and respond to the ECM through cell surface adhesion receptors such as integrins and mechanosensitive ion channels. While hematopoietic stem progenitor cells remain quiescent on stiffer ECM substrates, the maturation of the erythroid and megakaryocytic lineages occurs on softer ECM substrates. This review surveys the major matrix structural proteins that contribute to the overall biomechanical tone of the bone marrow, as well as key integrins and mechanosensitive ion channels identified as ECM sensors in context of megakaryocytosis or erythropoiesis.

Embryonic lineage tracing with Procr-CreER marks balanced hematopoietic stem cell fate during entire mouse lifespan

2019 ◽  
Vol 46 (10) ◽  
pp. 489-498 ◽  
Author(s):  
Xiaona Zheng ◽  
Guangyu Zhang ◽  
Yandong Gong ◽  
Xiaowei Ning ◽  
Zhijie Bai ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Hematopoietic Stem Cell ◽  
Lineage Tracing ◽  
Hematopoietic Stem ◽  
Stem Cell Fate
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