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Animal Stem Cells

Laminin-511 but not -332, -111, or -411 enables mouse embryonic stem cell self-renewal in vitro

Domogatskaya A., Rodin S., Boutaud A., Tryggvason K.
Stem Cells, 2008

Different laminin isoforms, LN-511, -332, -411 and -111, and Matrigel, gelatin and poly-D-lysine are compared as substrata maintaining pluripotent mouse ES cells in vitro without addition of leukemia inhibitory factor. Conclusions are that only LN-511 is able to sustain self-renewal for up to 169 days of culturing and cells maintain expression of pluripotency markers and can be used for generation of chimeric mice.


The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification

Boroviak T., Loos R., Bertone P., Smith A. and Nichols J.
Nature Cell Biology, 2014

The authors show that mouse ICM cells from early blastocysts can progress to ERK independence if provided with a specific laminin substrate. We show by RNA sequencing that Laminin-511 is expressed in the early ICM, as is B1-integrin, which mediates laminin binding in ESCs. No expression of Laminin-521 in mouse ICM. Single ESC derivation in 2i-LIF on a fibronectin-LN511 mix and clonal ESC lines expansion on LN511.


Enhanced reseeding of decellularized rodent lungs with mouse embryonic stem cells

Lecht S., Stabler C.T., Rylander A.L., Chiaverelli R., Schulman E.S., Marcinkiewicz C., Lelkes P.I.
Biomaterials, 2013

All current decellularization methodologies result in significant alterations of the contents, and ratios of ECM proteins, though the exact degree of the loss of ECM glycoproteins, such as laminins. Pre-treatment of decellularized matrices with defined ECM proteins, to evaluate the efficacy of reseeding of mESC. Following ECMs were tested: bovine collagen type IV; human collagen type IV; human pro-collagen type I; human collagen type I; rat collagen type I; human plasma-purified fibronectin (FN); human thrombospondin-1; VCAM; vitronectin; bovine elastin; Matrigel-purified laminin-111; and human recombinant laminins (LN) -111, -211, -332, -411, -421, -511, -521. mESCs lack major integrin receptors for collagens but express high levels of functional receptors for LN and FN. Laminin and FN appears to be the major pro-adhesive ECM protein for mESCs. They evaluated a series of recombinant LNs representing the diversity of isoforms present in the lung and evaluated their affinity towards mESCs adhesion. The mESCs were found to adhere differentially in an isoform-dependent manner with the following order of potencies 511 = 521 >332 >421 >211 >111 >411. These findings further support the notion that a3b1 and a6b1 integrin receptors expressed on the mES cell surface are involved in the specific binding to LN in general and to LN511 and -521.


Functional Diversity of Laminins

Domogatskaya A., Rodin S., Tryggvason K.
Annu Rev Cell Dev Biol., 2012 

This extensive review provides in-depth information on the molecular complexity of laminins and the current knowledge of their diversity and different functional roles. The review gives the reader an understanding of the importance of laminins for different cell- and tissue types in both normal and pathological functioning in mammals at different stages of development and function.