In vivo time-lapse imaging shows diverse niche engagement by quiescent and naturally activated hematopoietic stem cells.
Hematopoietic stem cells (HSCs) maintain the turnover of mature blood cells during steady state and in response to systemic perturbations such as infections. Their function critically depends on complex signal exchanges with the bone marrow (BM) microenvironment in which they reside, but the cellular mechanisms involved in HSC-niche interactions and regulating HSC function in vivo remain elusive. We used a natural mouse parasite, Trichinella spiralis, and multipoint intravital time-lapse confocal microscopy of mouse calvarium BM to test whether HSC-niche interactions may change when hematopoiesis is perturbed. We find that steady-state HSCs stably engage confined niches in the BM whereas HSCs harvested during acute infection are motile and therefore interact with larger niches. These changes are accompanied by increased long-term repopulation ability and expression of CD44 and CXCR4. Administration of a CXCR4 antagonist affects the duration of HSC-niche interactions. These findings suggest that HSC-niche interactions may be modulated during infection.
Department of Life Sciences, Imperial College London, London, United Kingdom; and.
Narges M
NM
Rashidi
Department of Life Sciences, Imperial College London, London, United Kingdom; and.
Mark K
MK
Scott
Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Nico
N
Scherf
Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Axel
A
Krinner
Department of Life Sciences, Imperial College London, London, United Kingdom; and.
Jens S
JS
Kalchschmidt
Department of Life Sciences, Imperial College London, London, United Kingdom; and.
Kleoniki
K
Gounaris
Department of Life Sciences, Imperial College London, London, United Kingdom; and.
Murray E
ME
Selkirk
Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Ingo
I
Roeder
Department of Life Sciences, Imperial College London, London, United Kingdom; and.
Cristina
C
Lo Celso
D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism; D055153:Stem Cell Niche / Q000502:physiology*; D059008:Time-Lapse Imaging; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000276:immunology / Q000378:metabolism*
C514936:CXCR4 protein, mouse; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D019718:Receptors, CXCR4