Enhanced engraftment of human haematopoietic stem cells via mechanical remodelling mediated by the corticotropin-releasing hormone

  • DeFilipp, Z., Hefazi, M., Chen, Y. B. & Blazar, B. R. Emerging approaches to improve allogeneic hematopoietic cell transplantation outcomes for nonmalignant diseases. Blood 139, 3583–3593 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Broxmeyer, H. E. Enhancing the efficacy of engraftment of cord blood for hematopoietic cell transplantation. Transfus. Apher. Sci. 54, 364–372 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lund, T. C., Boitano, A. E., Delaney, C. S., Shpall, E. J. & Wagner, J. E. Advances in umbilical cord blood manipulation—from niche to bedside. Nat. Rev. Clin. Oncol. 12, 163–174 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Bai, T. et al. Expansion of primitive human hematopoietic stem cells by culture in a zwitterionic hydrogel. Nat. Med. 25, 1566 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sakurai, M. et al. Chemically defined cytokine-free expansion of human haematopoietic stem cells. Nature 615, 127 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Omer-Javed, A. et al. Mobilization-based chemotherapy-free engraftment of gene-edited human hematopoietic stem cells. Cell 185, 2248–2264.e21 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Guo, B., Huang, X., Cooper, S. & Broxmeyer, H. E. Glucocorticoid hormone-induced chromatin remodeling enhances human hematopoietic stem cell homing and engraftment. Nat. Med. 23, 424–428 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, X., Guo, B., Liu, S., Wan, J. & Broxmeyer, H. E. Neutralizing negative epigenetic regulation by HDAC5 enhances human haematopoietic stem cell homing and engraftment. Nat. Commun. 9, 2741 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, D. et al. VCAM-1+ macrophages guide the homing of HSPCs to a vascular niche. Nature 564, 119–124 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Khurana, S. et al. Glypican-3-mediated inhibition of CD26 by TFPI: a novel mechanism in hematopoietic stem cell homing and maintenance. Blood 121, 2587–2595 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mei, Y. et al. Diaphanous-related formin mDia2 regulates beta2 integrins to control hematopoietic stem and progenitor cell engraftment. Nat. Commun. 11, 3172 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rak, J. et al. Cytohesin 1 regulates homing and engraftment of human hematopoietic stem and progenitor cells. Blood 129, 950–958 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mendelson, A. & Frenette, P. S. Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat. Med. 20, 833–846 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mantel, C. R. et al. Enhancing hematopoietic stem cell transplantation efficacy by mitigating oxygen shock. Cell 161, 1553–1565 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sun, X. et al. Nicotinamide riboside attenuates age-associated metabolic and functional changes in hematopoietic stem cells. Nat. Comm. 12, 2665 (2021).

  • Du, H. et al. Tuning immunity through tissue mechanotransduction. Nat. Rev. Immunol. 23, 174–188 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • De Belly, H., Paluch, E. K. & Chalut, K. J. Interplay between mechanics and signalling in regulating cell fate. Nat. Rev. Mol. Cell Biol. 23, 465–480 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Lomakin, A. J. et al. The nucleus acts as a ruler tailoring cell responses to spatial constraints. Science 370, eaba2894 (2020).

  • Vining, K. H. & Mooney, D. J. Mechanical forces direct stem cell behaviour in development and regeneration. Nat. Rev. Mol. Cell Biol. 18, 728–742 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dalby, M. J., García, A. J. & Salmeron-Sanchez, M. Receptor control in mesenchymal stem cell engineering. Nat. Rev. Mater. 3, 17091 (2018).

  • Shin, J. W. et al. Contractile forces sustain and polarize hematopoiesis from stem and progenitor cells. Cell Stem Cell 14, 81–93 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, P. et al. The physical microenvironment of hematopoietic stem cells and its emerging roles in engineering applications. Stem Cell Res. Ther. 10, 327 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, H. et al. Biomechanical cues as master regulators of hematopoietic stem cell fate. Cell. Mol. Life Sci. 78, 5881–5902 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, S., Shah, S. B., Graney, P. L. & Singh, A. Multiscale engineering of immune cells and lymphoid organs. Nat. Rev. Mater. 4, 355–378 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Biedzinski, S. et al. Microtubules control nuclear shape and gene expression during early stages of hematopoietic differentiation. EMBO J. 39, e103957 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ni, F. et al. Ptpn21 controls hematopoietic stem cell homeostasis and biomechanics. Cell Stem Cell 24, 608–620.e6 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • AbuZineh, K. et al. Microfluidics-based super-resolution microscopy enables nanoscopic characterization of blood stem cell rolling. Sci. Adv. 4, eaat5304 (2018).

  • Henckens, M. J., Deussing, J. M. & Chen, A. Region-specific roles of the corticotropin-releasing factor–urocortin system in stress. Nat. Rev. Neurosci. 17, 636–651 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Poller, W. C. et al. Brain motor and fear circuits regulate leukocytes during acute stress. Nature 607, 578–584 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Germain, L. et al. Preclinical models of prostate cancer – modelling androgen dependency and castration resistance in vitro, ex vivo and in vivo. Nat. Rev. Urol. 20, 480–493 (2023).

  • Androulidaki, A. et al. Corticotropin Releasing Factor promotes breast cancer cell motility and invasiveness. Mol. Cancer 8, 30 (2009).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Steidl, U. et al. Primary human CD34+ hematopoietic stem and progenitor cells express functionally active receptors of neuromediators. Blood 104, 81–88 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kalafati, L. & Chavakis, T. Hematopoietic stem and progenitor cells take the route through the bone marrow endothelium. Haematologica 105, 2700–2701 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bixel, M. G. et al. Flow dynamics and HSPC homing in bone marrow microvessels. Cell Rep. 18, 1804–1816 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kanchanawong, P. & Calderwood, D. A. Organization, dynamics and mechanoregulation of integrin-mediated cell-ECM adhesions. Nat. Rev. Mol. Cell Biol. 24, 142–161 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nurnberg, A., Kitzing, T. & Grosse, R. Nucleating actin for invasion. Nat. Rev. Cancer 11, 177–187 (2011).

    Article 
    PubMed 

    Google Scholar
     

  • De Belly, H. et al. Cell protrusions and contractions generate long-range membrane tension propagation. Cell 186, 3049–3061.e15 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kalukula, Y., Stephens, A. D., Lammerding, J. & Gabriele, S. Mechanics and functional consequences of nuclear deformations. Nat. Rev. Mol. Cell Biol. 23, 583–602 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Saraswathibhatla, A., Indana, D. & Chaudhuri, O. Cell-extracellular matrix mechanotransduction in 3D. Nat. Rev. Mol. Cell Biol. 24, 495–516 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Winkler, J., Abisoye-Ogunniyan, A., Metcalf, K. J. & Werb, Z. Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nat. Commun. 11, 5120 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yamashiro, Y. et al. Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP in the vascular remodeling. Proc. Natl Acad. Sci. USA 117, 9896–9905 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Risher, W. C. & Eroglu, C. Thrombospondins as key regulators of synaptogenesis in the central nervous system. Matrix Biol. 31, 170–177 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Muth, C. A., Steinl, C., Klein, G. & Lee-Thedieck, C. Regulation of hematopoietic stem cell behavior by the nanostructured presentation of extracellular matrix components. PLoS ONE 8, e54778 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yu, F. X. et al. Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell 150, 780–791 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nan, P. et al. Tumor-stroma TGF-β1-THBS2 feedback circuit drives pancreatic ductal adenocarcinoma progression via integrin αvβ3/CD36-mediated activation of the MAPK pathway. Cancer Lett. 528, 59–75 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • He, Z. C. et al. Identification of BGN and THBS2 as metastasis-specific biomarkers and poor survival key regulators in human colon cancer by integrated analysis. Clin. Transl. Med. 12, e973 (2022).

  • Calabro, N. E., Kristofik, N. J. & Kyriakides, T. R. Thrombospondin-2 and extracellular matrix assembly. Biochim. Biophys. Acta 1840, 2396–2402 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liesveld, J. L., Sharma, N. & Aljitawi, O. S. Stem cell homing: from physiology to therapeutics. Stem Cells 38, 1241–1253 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Kollet, O. et al. Physiologic corticosterone oscillations regulate murine hematopoietic stem/progenitor cell proliferation and CXCL12 expression by bone marrow stromal progenitors. Leukemia 27, 2006–2015 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gao, W. et al. Glucocorticoid guides mobilization of bone marrow stem/progenitor cells via FPR and CXCR4 coupling. Stem Cell Res. Ther. 12, 16 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Monzo, P. et al. Adaptive mechanoproperties mediated by the formin FMN1 characterize glioblastoma fitness for invasion. Dev. Cell 56, 2841–2855.e8 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gensbittel, V. et al. Mechanical adaptability of tumor cells in metastasis. Dev. Cell 56, 164–179 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cai, D. F. et al. Phase separation of YAP reorganizes genome topology for long-term YAP target gene expression. Nat. Cell Biol. 21, 1578 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hu, X. H. et al. Nuclear condensates of YAP fusion proteins alter transcription to drive ependymoma tumourigenesis. Nat. Cell Biol. 25, 323 (2023).

    CAS 
    PubMed 

    Google Scholar
     

  • Liao, X., Wang, W., Yu, B. & Tan, S. Thrombospondin-2 acts as a bridge between tumor extracellular matrix and immune infiltration in pancreatic and stomach adenocarcinomas: an integrative pan-cancer analysis. Cancer Cell Int. 22, 213 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Carminati, L. & Taraboletti, G. Thrombospondins in bone remodeling and metastatic bone disease. Am. J. Physiol. Cell Physiol. 319, C980–C990 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Shi, H. et al. Bone marrow-derived mesenchymal stem cells promote Helicobacter pylori-associated gastric cancer progression by secreting thrombospondin-2. Cell Prolif. 54, e13114 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Inoue, A. et al. Illuminating G-protein-coupling selectivity of GPCRs. Cell 177, 1933–1947.e25 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, Y. et al. Impairment of synaptic plasticity by the stress mediator CRH involves selective destruction of thin dendritic spines via RhoA signaling. Mol. Psychiatry 18, 485–496 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Morrison, S. J. & Scadden, D. T. The bone marrow niche for haematopoietic stem cells. Nature 505, 327–334 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wilkinson, A. C., Igarashi, K. J. & Nakauchi, H. Haematopoietic stem cell self-renewal in vivo and ex vivo. Nat. Rev. Genet. 21, 541–554 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liggett, L. A. & Sankaran, V. G. Unraveling hematopoiesis through the lens of genomics. Cell 182, 1384–1400 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Le Berre, M., Zlotek-Zlotkiewicz, E., Bonazzi, D., Lautenschlaeger, F. & Piel, M. Methods for two-dimensional cell confinement. Methods Cell. Biol. 121, 213–229 (2014).

    Article 
    PubMed 

    Google Scholar
     

  • Fay, M. E. et al. Cellular softening mediates leukocyte demargination and trafficking, thereby increasing clinical blood counts. Proc. Natl Acad. Sci. USA 113, 1987–1992 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Holtmaat, A. et al. Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window. Nat. Protoc. 4, 1128–1144 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shih, A. Y. et al. Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain. J. Cereb. Blood Flow Metab. 32, 1277–1309 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liang T. CRH_RNAseq. GitHub https://github.com/Tility/CRH_RNAseq (2024).