Starting with multipotent progenitors, hematopoietic lineages are specified by lineage-restricted transcription factors. The transcription factors that determine the decision between lymphoid and myeloid cell fates, and the underlying mechanisms, remain largely unknown. Here, we report that enforced expression of C/EBPalpha and C/EBPbeta in differentiated B cells leads to their rapid and efficient reprogramming into macrophages. C/EBPs induce these changes by inhibiting the B cell commitment transcription factor Pax5, leading to the downregulation of its target CD19, and synergizing with endogenous PU.1, an ETS family factor, leading to the upregulation of its target Mac-1 and other myeloid markers. The two processes can be uncoupled, since, in PU.1-deficient pre-B cells, C/EBPs induce CD19 downregulation but not Mac-1 activation. Our observations indicate that C/EBPalpha and beta remodel the transcription network of B cells into that of macrophages through a series of parallel and sequential changes that require endogenous PU.1.
We demonstrate here that "promiscuous" expression of myeloid or lymphoid genes precedes lineage commitment in hematopoiesis. Prospectively purified single common myeloid progenitors (CMPs) coexpress myelo-erythroid but not lymphoid genes, whereas single common lymphoid progenitors (CLPs) coexpress T and B lymphoid but not myeloid genes. Genes unrelated to the adopted lineage are downregulated in bipotent and monopotent descendants of CMPs and CLPs. Promiscuous gene expression does not alter the biological potential of multipotent progenitors: CMPs with an activated endogenous M lysozyme locus yield normal proportions of myelo-erythroid colonies, and CLPs expressing the pre-T cell receptor alpha gene differentiate into normal numbers of B cells. Thus, the accessibility for multiple myeloid or lymphoid programs promiscuously may allow flexibility in fate commitments at these multipotent stages.
Maximum distance separable (MDS) codes are optimal error-correcting codes in the sense that they provide the maximum failure-tolerance for a given number of parity nodes. Suppose that an MDS code with k information nodes and r " n´k parity nodes is used to encode data in a distributed storage system. It is known that if h out of the n nodes are inaccessible and d surviving (helper) nodes are used to recover the lost data, then we need to download at least h{pd`h´kq fraction of the data stored in each of the helper nodes (Dimakis et al., 2010 and. If this lower bound is achieved for the repair of any h erased nodes from any d helper nodes, we say that the MDS code has the ph, dq-optimal repair property.We study high-rate MDS array codes with the optimal repair property. Explicit constructions of such codes in the literature are only available for the cases where there are at most 3 parity nodes, and these existing constructions can only optimally repair a single node failure by accessing all the surviving nodes.In this paper, given any r and n, we present two explicit constructions of MDS array codes with the ph, dq-optimal repair property for all h ď r and k ď d ď n´h simultaneously. Codes in the first family can be constructed over any base field F as long as |F | ě sn, where s " lcmp1, 2, . . . , rq. The encoding, decoding, repair of failed nodes, and update procedures of these codes all have low complexity. Codes in the second family have the optimal access property and can be constructed over any base field F as long as |F | ě n`1. Moreover, both code families have the optimal error resilience capability when repairing failed nodes. We also construct several other related families of MDS codes with the optimal repair property.The authors are with
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.