Pluripotency-independent induction of human trophoblast stem cells from fibroblasts.

Human trophoblast stem cells (hTSCs) can be derived from embryonic stem cells (hESCs) or be induced from somatic cells by OCT4, SOX2, KLF4 and MYC (OSKM). Here we explore whether the hTSC state can be induced independently of pluripotency, and what are the mechanisms underlying its acquisition. We identify GATA3, OCT4, KLF4 and MYC (GOKM) as a combination of factors that can generate functional hiTSCs from fibroblasts. Transcriptomic analysis of stable GOKM- and OSKM-hiTSCs reveals 94 hTSC-specific genes that are aberrant specifically in OSKM-derived hiTSCs. Through time-course-RNA-seq analysis, H3K4me2 deposition and chromatin accessibility, we demonstrate that GOKM exert greater chromatin opening activity than OSKM. While GOKM primarily target hTSC-specific loci, OSKM mainly induce the hTSC state via targeting hESC and hTSC shared loci. Finally, we show that GOKM efficiently generate hiTSCs from fibroblasts that harbor knockout for pluripotency genes, further emphasizing that pluripotency is dispensable for hTSC state acquisition.

Ehrlichia canis morulae in peripheral blood lymphocytes of two naturally-infected puppies in Israel.

Ehrlichia canis is the major causative agent of canine monocytic ehrlichiosis (CME). Its morulae might be detected during the acute disease phase, usually within peripheral blood monocytes, but were uncommonly described within peripheral blood lymphocytes. This report describes two unrelated puppies, naturally infected with E. canis. In both, examination of stained peripheral blood smears revealed one to several cytoplasmic inclusions, characteristic of typical E. canis morulae, exclusively within lymphocytes. Ehrlichia canis infection was confirmed in both cases by blood sample real-time PCR. Both dogs were young and had comorbidities. One dog, based on whole blood PCR, was co-infected with Anaplasma platys and Babesia vogeli. The other had no other concurrent tick-borne infection based on PCR, but had bacterial cholangiohepatitis. These comorbidities, and the dogs' young age possibly contributed to the uncommon presence of E. canis morulae within peripheral blood lymphocytes rather than their typical presence in monocytes.