Department of Cell Biology and Human Anatomy, University of California, Davis, CA 95616, USA; Institute of Pediatric Regenerative Medicine, Shriners Hospital for Children Northern California, Sacramento, CA 95817, USA; Genome Center, University of California, Davis, CA 95616, USA.
Department of Cell Biology and Human Anatomy, University of California, Davis, CA 95616, USA; Institute of Pediatric Regenerative Medicine, Shriners Hospital for Children Northern California, Sacramento, CA 95817, USA; Genome Center, University of California, Davis, CA 95616, USA.
Stem Cell Reports. 2021 Dec 14;16(12):2844-2851. doi: 10.1016/j.stemcr.2021.10.008. Epub 2021 Nov 11.
Many gene networks are shared between pluripotent stem cells and cancer; a concept exemplified by several DPPA factors such as DPPA2 and DPPA4, which are highly and selectively expressed in stem cells but also found to be reactivated in cancer. Despite their striking expression pattern, for many years the function of DPPA2 and DPPA4 remained a mystery; knockout of Dppa2 and Dppa4 did not affect pluripotency, but caused lung and skeletal defects late in development, long after Dppa2 and Dppa4 expression had been turned off. A number of recent papers have further clarified and defined the roles of these important factors, identifying roles in priming the chromatin and maintaining developmental competency through regulating both H3K4me3 and H3K27me3 at bivalent chromatin domains, and acting to remodel chromatin and facilitate reprogramming of somatic cells to induced pluripotency. These findings highlight an important regulatory role for DPPA2 and DPPA4 at the transitional boundary between pluripotency and differentiation and may have relevance to the functions of DPPA2 and 4 in the context of cancer cells as well.
许多基因网络在多能干细胞和癌症之间共享；这一概念的一个例子是几个 DPPA 因子，如 DPPA2 和 DPPA4，它们在干细胞中高度且选择性表达，但也在癌症中被发现重新激活。尽管它们的表达模式引人注目，但多年来 DPPA2 和 DPPA4 的功能仍然是一个谜；Dppa2 和 Dppa4 的敲除并不影响多能性，但会导致肺部和骨骼缺陷，这是在 Dppa2 和 Dppa4 表达关闭很久之后发生的。最近的一些论文进一步阐明和定义了这些重要因子的作用，确定了它们在启动染色质方面的作用，并通过调节二价染色质区域的 H3K4me3 和 H3K27me3 来维持发育能力，还可以重塑染色质，并促进体细胞重编程为诱导多能性。这些发现强调了 DPPA2 和 DPPA4 在多能性和分化之间的过渡边界的重要调节作用，并且在癌细胞的背景下，DPPA2 和 4 的功能可能也具有相关性。
