Recently, direct reprogramming between divergent lineages has been achieved by the introduction of regulatory transcription factors. This approach may provide alternative cell resources for drug discovery and regenerative medicine, but applications could be limited by the genetic manipulation involved. Here, we show that mouse fibroblasts can be directly converted into neuronal cells using only a cocktail of small molecules, with a yield of up to >90% being TUJ1-positive after 16 days of induction. After a further maturation stage, these chemically induced neurons (CiNs) possessed neuron-specific expression patterns, generated action potentials, and formed functional synapses. Mechanistically, we found that a BET family bromodomain inhibitor, I-BET151, disrupted the fibroblast-specific program, while the neurogenesis inducer ISX9 was necessary to activate neuron-specific genes. Overall, our findings provide a "proof of principle" for chemically induced direct reprogramming of somatic cell fates across germ layers without genetic manipulation, through disruption of cell-specific programs and induction of an alternative fate.

Highlights d H2-T6SS mediates molybdate acquisition by secretion of ModA d Expression of H2-T6SS is activated by the master regulator Anr and anaerobiosis d ModA interacts with the outer membrane protein IcmP and uses it to deliver molybdate d The T6SS-ModA-IcmP system plays a role for P. aeruginosa

Although green innovation strategy (GIS) is the driving force for the sustainable development of enterprises, while the strategy is implemented, an increased cost and a change in organizational routines will cause an organization to become fragile, and even affect the sustainable competitive advantages. So, the purpose of this paper is to explore the impact path of GIS on sustainable competitive advantages and the implementation boundary of GIS. To explain the impact path, we consider the concept of dynamic capabilities to be the mediator variable. To explain the implementation boundary of GIS, we systematically explore the relationships among GIS, dynamic capabilities and sustainable competitive advantages under different levels of environmental uncertainty. Based on 241 new Chinese green firms, the empirical results find that GIS helps enterprises to gain sustainable competitive advantages. However, in the process of strategy implementation, enterprises should choose appropriate methods according to different degrees of environmental uncertainty. In a low environmental uncertainty, dynamic capabilities play a full intermediary role between GIS and sustainable competitive advantages. However, in a high environmental uncertainty, dynamic capabilities have no mediating effect between GIS and sustainable competitive advantages. This study not only integrates green management theory and strategic management theory but also makes up for the deficiencies in research on these theories and has important reference value for enterprises that seek to carry out green innovation activities.