Leukemia Inhibitory Factor (LIF) Protein

Leukemia Inhibitory Factor (LIF) belongs to the interleukin-6 cytokine family. LIF binds to a heterodimeric receptor consisting of the low-affinity LIF receptor and gp130, with downstream signals being transmitted through gp130. There are a number of signaling pathways downstream of gp130, including the STAT3, phosphatidylinositol 3-kinase (PI3K) and Ras/Erk pathways. In the STAT3 pathway, signaling through gp130 leads to activation of Janus-associated tyrosine kinases (JAKs), which in turn phosphorylate STAT3. Phosphorylated STAT3 dimerizes and translocates to the nucleus, where it functions as a transcription factor activating pluripotency factors such as Oct-4, Nanog and Sox-2. LIF also has the capacity to induce terminal differentiation of leukemic cells, hematopoietic differentiation in myeloid leukemia cells, neuronal cell differentiation, and stimulate acute-phase protein synthesis in hepatocytes.

Use in Stem Cell Culture

LIF is normally expressed in the trophectoderm of the developing embryo, with its receptor LIFR expressed throughout the inner cell mass. As embryonic stem cells are derived from the inner cell mass at the blastocyst stage, removing them from the inner cell mass also removes their source of LIF. Thus, recombinant LIF protein is often added to stem cell culture media as an alternative to feeder and FBS supplemented media. Mouse LIF (mLIF) promotes the self-renewal and long-term maintenance of mouse ES cells while Human LIF (hLIF) induces proliferation of human neural progenitor cells.

Alkaline Phosphatase staining of Mouse ES cells. (A) Undifferentiated ES cells cultured for five days in media containing LIF/ESGRO^®. A concentration of 10³ Units/mL is used for inhibition of differentiation. (B) Differentiated ES cells – cultured at low-medium density for three days in media without any LIF/ESGRO^®. (C) Differentiated ES cells – cultured at low-medium density for six days in media without any LIF/ESGRO^®.