Cheng L, Gearing D P, White L S, Compton D L, Schooley K, Donovan P J
ABL-Basic Research Program, NCI-FCRDC, Frederick, Maryland 21702-1201.
Development. 1994 Nov;120(11):3145-53. doi: 10.1242/dev.120.11.3145.
The pleiotropic cytokine leukemia inhibitory factor (LIF) is able to promote the growth of mouse primordial germ cells (PGCs) in culture. It is unclear whether LIF acts directly on PGCs or indirectly via feeder cells or embryonic somatic cells. To understand the role of LIF in PGC growth, we have carried out molecular and cell culture analyses to investigate the role of both the LIF ligand and its receptor in PGC development. LIF is able to stimulate PGC growth independently of the presence of feeder cells supporting the hypothesis that LIF acts directly on PGCs to promote their growth. We show here that transcripts for the low-affinity LIF receptor (LIFR), an integral component of the functional LIF receptor complex, are expressed in the developing gonad. Fluorescence-activated cell sorter (FACS) analysis, using an anti-LIFR antiserum, demonstrates that LIFR is present on the surface of PGCs, suggesting that PGCs are likely to be a direct target of LIF action in culture. Signalling via LIFR is essential for PGC growth in culture since the anti-LIFR antiserum, which blocks LIF binding to its receptor, abolishes PGC survival in culture. Two LIF-related cytokines, namely oncostatin M and ciliary neurotrophic factor, can also promote PGC growth in culture in addition to LIF. Thus one or more of these LIFR-dependent cytokines may play an important role in PGC development in mice.
多效性细胞因子白血病抑制因子（LIF）能够促进培养的小鼠原始生殖细胞（PGC）生长。目前尚不清楚LIF是直接作用于PGC，还是通过饲养细胞或胚胎体细胞间接发挥作用。为了了解LIF在PGC生长中的作用，我们进行了分子和细胞培养分析，以研究LIF配体及其受体在PGC发育中的作用。LIF能够独立于支持LIF直接作用于PGC以促进其生长这一假设的饲养细胞的存在来刺激PGC生长。我们在此表明，低亲和力LIF受体（LIFR）的转录本，即功能性LIF受体复合物的一个组成部分，在发育中的性腺中表达。使用抗LIFR抗血清的荧光激活细胞分选仪（FACS）分析表明，LIFR存在于PGC表面，这表明PGC可能是培养中LIF作用的直接靶点。由于阻断LIF与其受体结合的抗LIFR抗血清会消除培养中PGC的存活，因此通过LIFR的信号传导对于培养中PGC的生长至关重要。除了LIF之外，两种与LIF相关的细胞因子，即抑瘤素M和睫状神经营养因子，也能够促进培养中PGC的生长。因此，这些依赖LIFR的细胞因子中的一种或多种可能在小鼠PGC发育中发挥重要作用。
