Mouse gastrulation: Coordination of tissue patterning, specification and diversification of cell fate.

During mouse embryonic development a mass of pluripotent epiblast tissue is transformed during gastrulation to generate the three definitive germ layers: endoderm, mesoderm, and ectoderm. During gastrulation, a spatiotemporally controlled sequence of events results in the generation of organ progenitors and positions them in a stereotypical fashion throughout the embryo. Key to the correct specification and differentiation of these cell fates is the establishment of an axial coordinate system along with the integration of multiple signals by individual epiblast cells to produce distinct outcomes.

A Watershed Finding for Heart Regeneration.

The adult mammalian heart is minimally regenerative after injury, whereas neonatal hearts fully recover even after major damage. New work from the Red-Horse and Woo labs (Das et al., 2019) shows that collateral artery formation is a key mechanism contributing to successful regeneration in newborn mice and provides insights into how collateral arteries form.

Bioengineering an electro-mechanically functional miniature ventricular heart chamber from human pluripotent stem cells.

Tissue engineers and stem cell biologists have made exciting progress toward creating simplified models of human heart muscles or aligned monolayers to help bridge a longstanding gap between experimental animals and clinical trials. However, no existing human in vitro systems provide the direct measures of cardiac performance as a pump. Here, we developed a next-generation in vitro biomimetic model of pumping human heart chamber, and demonstrated its capability for pharmaceutical testing.

Embryonic maturation of epidermal Merkel cells is controlled by a redundant transcription factor network.

Merkel cell-neurite complexes are located in touch-sensitive areas of the mammalian skin and are involved in recognition of the texture and shape of objects. Merkel cells are essential for these tactile discriminations, as they generate action potentials in response to touch stimuli and induce the firing of innervating afferent nerves. It has been shown that Merkel cells originate from epidermal stem cells, but the cellular and molecular mechanisms of their development are largely unknown.

Epigenetic regulation of epidermal differentiation.

In a cell, the chromatin state is controlled by the highly regulated interplay of epigenetic mechanisms ranging from DNA methylation and incorporation of different histone variants to posttranslational modification of histones and ATP-dependent chromatin remodeling. These changes alter the structure of the chromatin to either facilitate or restrict the access of transcription machinery to DNA. These epigenetic modifications function to exquisitely orchestrate the expression of different genes, and together constitute the epigenome of a cell.

Polycomb subunits Ezh1 and Ezh2 regulate the Merkel cell differentiation program in skin stem cells.

While the Polycomb complex is known to regulate cell identity in ES cells, its role in controlling tissue-specific stem cells is not well understood. Here we show that removal of Ezh1 and Ezh2, key Polycomb subunits, from mouse skin results in a marked change in fate determination in epidermal progenitor cells, leading to an increase in the number of lineage-committed Merkel cells, a specialized subtype of skin cells involved in mechanotransduction. By dissecting the genetic mechanism, we showed that the Polycomb complex restricts differentiation of epidermal progenitor cells by repressing the transcription factor Sox2.

SWItching on epidermal cell fate.

Chromatin regulatory complexes are well known regulators of stem cell fate; however, the mechanisms regulating their activity are not well understood. In this issue of Cell Stem Cell, Bao et al. (2013) show that ACTL6a inhibits targeting of the SWI/SNF complex to differentiation genes, thereby preserving the epidermal progenitor state.

Epigenetic regulation of skin: focus on the Polycomb complex.

Chromatin regulators have recently emerged as key players in the control of tissue development and tumorigenesis. One specific chromatin regulator, the Polycomb complex, has been shown to regulate the identity of embryonic stem cells, but its role in controlling fates of multipotent progenitors in developing tissues is still largely unknown. Recent findings have revealed that this complex plays a critical role in control of skin stem cell renewal and differentiation.