Author
Listed:
- Constantina Christodoulou
(Boston Children’s Hospital
Harvard University
Novartis Institutes for BioMedical Research)
- Joel A. Spencer
(Massachusetts General Hospital
Massachusetts General Hospital
Massachusetts General Hospital
University of California Merced)
- Shu-Chi A. Yeh
(Massachusetts General Hospital
Massachusetts General Hospital)
- Raphaël Turcotte
(Massachusetts General Hospital
Massachusetts General Hospital)
- Konstantinos D. Kokkaliaris
(ETH Zurich)
- Riccardo Panero
(University of Torino)
- Azucena Ramos
(Boston Children’s Hospital
Harvard University)
- Guoji Guo
(Howard Hughes Medical Institute, Harvard Medical School)
- Negar Seyedhassantehrani
(University of California Merced)
- Tatiana V. Esipova
(University of Pennsylvania
University of Pennsylvania)
- Sergei A. Vinogradov
(University of Pennsylvania
University of Pennsylvania)
- Sarah Rudzinskas
(University of Rochester Medical Center)
- Yi Zhang
(University of Rochester Medical Center)
- Archibald S. Perkins
(University of Rochester Medical Center)
- Stuart H. Orkin
(Howard Hughes Medical Institute, Harvard Medical School)
- Raffaele A. Calogero
(University of Torino)
- Timm Schroeder
(ETH Zurich)
- Charles P. Lin
(Massachusetts General Hospital
Massachusetts General Hospital)
- Fernando D. Camargo
(Boston Children’s Hospital
Harvard University)
Abstract
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.
Suggested Citation
Constantina Christodoulou & Joel A. Spencer & Shu-Chi A. Yeh & Raphaël Turcotte & Konstantinos D. Kokkaliaris & Riccardo Panero & Azucena Ramos & Guoji Guo & Negar Seyedhassantehrani & Tatiana V. Esip, 2020.
"Live-animal imaging of native haematopoietic stem and progenitor cells,"
Nature, Nature, vol. 578(7794), pages 278-283, February.
Handle:
RePEc:nat:nature:v:578:y:2020:i:7794:d:10.1038_s41586-020-1971-z
DOI: 10.1038/s41586-020-1971-z
Download full text from publisher
As the access to this document is restricted, you may want to search for a different version of it.
Citations
Citations are extracted by the
CitEc Project, subscribe to its
RSS feed for this item.
Cited by:
- Yinghui Li & Mei He & Wenshan Zhang & Wei Liu & Hui Xu & Ming Yang & Hexiao Zhang & Haiwei Liang & Wenjing Li & Zhaozhao Wu & Weichao Fu & Shiqi Xu & Xiaolei Liu & Sibin Fan & Liwei Zhou & Chaoqun Wan, 2023.
"Expansion of human megakaryocyte-biased hematopoietic stem cells by biomimetic Microniche,"
Nature Communications, Nature, vol. 14(1), pages 1-16, December.
- S-C. A. Yeh & J. Hou & J. W. Wu & S. Yu & Y. Zhang & K. D. Belfield & F. D. Camargo & C. P. Lin, 2022.
"Quantification of bone marrow interstitial pH and calcium concentration by intravital ratiometric imaging,"
Nature Communications, Nature, vol. 13(1), pages 1-13, December.
- Runfeng Miao & Harim Chun & Xing Feng & Ana Cordeiro Gomes & Jungmin Choi & João P. Pereira, 2022.
"Competition between hematopoietic stem and progenitor cells controls hematopoietic stem cell compartment size,"
Nature Communications, Nature, vol. 13(1), pages 1-12, December.
- Yang Liu & Qi Chen & Hyun-Woo Jeong & Bong Ihn Koh & Emma C. Watson & Cong Xu & Martin Stehling & Bin Zhou & Ralf H. Adams, 2022.
"A specialized bone marrow microenvironment for fetal haematopoiesis,"
Nature Communications, Nature, vol. 13(1), pages 1-16, December.
- Raquel S. Pereira & Rahul Kumar & Alessia Cais & Lara Paulini & Alisa Kahler & Jimena Bravo & Valentina R. Minciacchi & Theresa Krack & Eric Kowarz & Costanza Zanetti & Parimala Sonika Godavarthy & Fa, 2023.
"Distinct and targetable role of calcium-sensing receptor in leukaemia,"
Nature Communications, Nature, vol. 14(1), pages 1-19, December.
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:578:y:2020:i:7794:d:10.1038_s41586-020-1971-z. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.