During mammalian embryonic development, a series of complex but precisely regulated decisions guide cells towards specific lineages and maintain pluripotency within the inner cell mass (ICM). Central to these processes is a network of transcription factors that orchestrate gene expression patterns critical for cell fate determination.

One well-established fact is that pluripotency within the ICM is maintained by the cooperative action of three core transcription factors: Oct4, Sox2, and Nanog. These factors form a regulatory circuit that sustains self-renewal and prevents premature differentiation of embryonic stem cells derived from the ICM.

Before blastocyst formation, individual blastomeres express both Oct4 and Cdx2 transcription factors. This co-expression indicates that these cells retain the potential to differentiate into either the ICM or the trophoblast lineage, reflecting developmental plasticity at this stage.

However, lineage segregation is accompanied by differential expression: Cdx2 becomes predominantly expressed in trophoblast cells, driving trophectoderm differentiation, while Oct4 expression is retained in the ICM to uphold pluripotency and prevent trophoblast fate adoption.

Importantly, Oct4 does not activate Cdx2; rather, these factors mutually inhibit one another to direct cell fate decisions, leading cells to become either ICM or trophoblast.

Therefore, of the provided statements:

• (A) Pluripotency of inner cell mass is maintained by a core of three transcription factors, Oct4, Sox2, and Nanog. (True)

• (B) Prior to blastocyst formation, each blastomere expresses both Cdx2 and Oct4 transcription factors and appears capable of becoming either ICM or trophoblast. (True)

• (C) Both ICM and trophoblast cells synthesize transcription factor Cdx2. (False; mainly trophoblast expresses Cdx2)

• (D) Oct4 activates Cdx2 expression enabling some cells to become trophoblast and others to become ICM. (False; Oct4 and Cdx2 are antagonistic)

Hence, the correct combination of true statements is:

(1) A and B

This understanding provides vital insight into the molecular mechanisms underlying early embryonic lineage specification and pluripotency maintenance in mammals.

Answer: (1) A and B