التفاصيل البيبلوغرافية
| العنوان: |
Live-animal imaging of native haematopoietic stem and progenitor cells |
| المؤلفون: |
Christodoulou, Constantina, Spencer, Joel A, Yeh, Shu-Chi A, Turcotte, Raphaël, Kokkaliaris, Konstantinos D, Panero, Riccardo, Ramos, Azucena, Guo, Guoji, Seyedhassantehrani, Negar, Esipova, Tatiana V, Vinogradov, Sergei A, Rudzinskas, Sarah, Zhang, Yi, Perkins, Archibald S, Orkin, Stuart H, Calogero, Raffaele A, Schroeder, Timm, Lin, Charles P, Camargo, Fernando D |
| المصدر: |
Nature, vol 578, iss 7794 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2020 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Transplantation, Stem Cell Research, Stem Cell Research - Nonembryonic - Human, Regenerative Medicine, Stem Cell Research - Nonembryonic - Non-Human, Underpinning research, 1.1 Normal biological development and functioning, Animals, Bone Remodeling, Cell Movement, Cell Proliferation, Cell Survival, Female, Genes, Reporter, Hematopoietic Stem Cells, Hypoxia, MDS1 and EVI1 Complex Locus Protein, Male, Mice, Molecular Imaging, Oxygen, Skull, fms-Like Tyrosine Kinase 3, General Science & Technology |
| جغرافية الموضوع: |
278 - 283 |
| الوصف: |
The biology of haematopoietic stem cells (HSCs) has predominantly been studied under transplantation conditions1,2. It has been particularly challenging to study dynamic HSC behaviour, given that the visualization of HSCs in the native niche in live animals has not, to our knowledge, been achieved. Here we describe a dual genetic strategy in mice that restricts reporter labelling to a subset of the most quiescent long-term HSCs (LT-HSCs) and that is compatible with current intravital imaging approaches in the calvarial bone marrow3-5. We show that this subset of LT-HSCs resides close to both sinusoidal blood vessels and the endosteal surface. By contrast, multipotent progenitor cells (MPPs) show greater variation in distance from the endosteum and are more likely to be associated with transition zone vessels. LT-HSCs are not found in bone marrow niches with the deepest hypoxia and instead are found in hypoxic environments similar to those of MPPs. In vivo time-lapse imaging revealed that LT-HSCs at steady-state show limited motility. Activated LT-HSCs show heterogeneous responses, with some cells becoming highly motile and a fraction of HSCs expanding clonally within spatially restricted domains. These domains have defined characteristics, as HSC expansion is found almost exclusively in a subset of bone marrow cavities with bone-remodelling activity. By contrast, cavities with low bone-resorbing activity do not harbour expanding HSCs. These findings point to previously unknown heterogeneity within the bone marrow microenvironment, imposed by the stages of bone turnover. Our approach enables the direct visualization of HSC behaviours and dissection of heterogeneity in HSC niches. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt1n90468c; https://escholarship.org/uc/item/1n90468cTest |
| الإتاحة: |
https://escholarship.org/uc/item/1n90468cTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.AEC79696 |
| قاعدة البيانات: |
BASE |
