Migration in CD34+ Human Cord Blood Hematopoietic stem/progenitor cells

Role of migration in Hematopoietic Stem/Progenitor Cells

Hematopoietic Stem Cells (HSC), as we mentioned in our previous post featuring mitosis in CD34+ Human Cord Blood HSC (https://nanolive.ch/cd34-mitosis/), are multipotent cells that can differentiate into a variety of blood cell types[1].

Migration plays a key role in HSCs, in both embryonic development and adult life. While in embryonic development, HSCs colonize different hematopoietic organs, in adulthood, migration helps maintain homeostasis of the hematopoietic system, and it takes part of innate immune responses[2].

Rear pole and leading edge in migrating HSCs

HSCs cytoplasmic and membrane constituents (proteins and lipids) are highly polarized[3]. This fate leads to the formation of the uropod, a specialized subcellular structure generally found at the rear pole. The uropod is involved in motility, intercellular adhesion and cell-cell communication[4], [5]. Migrating HSCs present a leading edge as well[4].

The uropod and the leading edge carry out opposite actions at the opposite cell extremities, resulting in a continuous attachment and de-adhesion cycle that leads to a net cell movement[4]–[6]. While the uropod is retracted at the rear pole, lamellipodium extension can be observed at the leading edge[4].

Observation of migration in an umbilical cord blood isolated CD34+ HSC sample

A sample of human cord blood CD34+ stem/progenitor cells kindly provided by Lonza was cultured in X-VIVOTM 15 serum-free hematopoietic cell medium, supplemented with recombinant human thrombopoietin (25ng/mL), Rlt3 ligand (25ng/mL) and stem cell factor (13ng/mL). The culture was also coated with fibronectin, and images were taken every 20s for 1 hour and 30 minutes under Nanolive’s 3D Cell Explorer.

Thanks to an optimal medium and freezing procedures, to the homogeneity of the cell culture and to Nanolive’s non-invasive and label-free technology, that allows for the observation of such sensitive cell types, we were able to capture cell movements and, in general, healthy cell culture behaviors. Such movements started with an active protruding leading edge acting against an attachment pod (the uropod) (Figure 1).

Taking into consideration the lack of CD34+ HSC movies, we could only compare such behavior to the one observed in lymphocytes, not just in the migrating mechanism, but also in the cellular shape, as HSCs also present a nucleus to cytoplasm ratio close to one.

[1]         “5. Hematopoietic Stem Cells | stemcells.nih.gov.” [Online]. Available: https://stemcells.nih.gov/info/2001report/chapter5.htm.

[2]         I. B. Mazo, S. Massberg, and U. H. von Andrian, “Hematopoietic stem and progenitor cell trafficking.,” Trends Immunol., vol. 32, no. 10, pp. 493–503, Oct. 2011.

[3]         J. Woodward, “Regulation of haematopoietic progenitor cell proliferation and survival: The involvement of the osteoblast.,” Cell Adh. Migr., vol. 4, no. 1, pp. 4–6, 2010.

[4]         A.-V. Fonseca and D. Corbeil, “The hematopoietic stem cell polarization and migration: A dynamic link between RhoA signaling pathway, microtubule network and ganglioside-based membrane microdomains.,” Commun. Integr. Biol., vol. 4, no. 2, pp. 201–4, Mar. 2011.

[5]         F. Sánchez-Madrid and J. M. Serrador, “Bringing up the rear: defining the roles of the uropod,” Nat. Rev. Mol. Cell Biol., vol. 10, no. 5, pp. 353–359, May 2009.

[6]         “Stem Cells Get A Grip — ScienceDaily.” [Online]. Available: https://www.sciencedaily.com/releases/2006/12/061215091126.htm. [Accessed: 23-Sep-2019].

 

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