Recent studies show why stem cells need full-length laminin

The first protein in the pluripotent stem cell niche: laminin-521

A recent publication by Rosner et al. (2024) in Developmental Cell identifies laminin-521 (LN521) as a critical component of the basement membrane (BM) during human embryogenesis. The basement membrane is a specialized layer of extracellular matrix that provides structural support, regulates cell behavior, and is essential for cell survival, differentiation, and tissue organization.

Key findings from Rosner et al. include:

• LN521 is the first and foundational component of the embryonic BM, supporting stem cells from the earliest stages
• Once produced, LN521 binds directly to cell surfaces and self-assembles into an independent network.
• LN521 regulates cell differentiation and tissue development from the early stages of embryogenesis.

The study also reports that Oct4 regulates laminin assembly via Rac1 and Akt signaling pathways.

Proper formation and maintenance of these laminin-containing BMs are crucial for tissue formation during early human development.

What about other laminin isoforms?

The study notes an interspecies difference between the human and mouse pluripotent stem cell (PSC) niche: laminin-511 (LN511, which contains the beta1 chain) is specific to mice, in comparison to LN521 (beta2) in human. Thus, laminin-511 isoform is only biologically relevant in murine models, not for human PSCs. Additionally, the study notes that laminin-111 (LN111) is restricted to the outer layer of the human embryo (Bruchert’s membrane) and therefore holds no significance for human PSCs.

Full-length laminins: essential for proper cell-ECM interactions

Full-length laminin means full functionality

A recent comprehensive review by renowned laminin experts Yurchenko and Kulczyk (2024) in Journal of Biological Chemistry explains how full-length laminins self-assemble and interact with extracellular matrix (ECM) components and various receptors on the cell membrane. These interactions are critical for maintaining tissue integrity and supporting cellular functions.

Minor changes in laminin composition can cause diseases such as muscular dystrophy and Pierson syndrome, underscoring the need for intact, full-length laminin to support healthy tissues.

Key aspects of full-length laminins include:

• Polymerization and assembly: Full-length laminins are necessary for proper basement membrane formation, establishing stable networks that support cell function.
• Comprehensive interactions: Only full-length laminins bind all relevant receptors (such as dystroglycans and syndecans), other ECM components (like perlecan and nidogen), and growth factors (such as VEGF).
• Functional domains: Full-length laminins retain critical domains for versatile interactions with other ECM proteins, which are missing in truncated forms.

These findings show that only full-length laminin-521 can accurately replicate the natural stem cell environment in vitro.